|
Regimen to promote neuroprotection and encourage
nerve repair
(plus a compendium of resources and promising
adjunctive therapeutic agents for Multiple Sclerosis and other neurological
diseases & disorders)
Printable PDF format version
Dr. Anthony G. Payne
E-mail: Biotheoretician@gmail.com
Suggested regimen to help quell inflammation
and promote nerve repair in various neurodegenerative and neuroinflammatory
diseases and disorders
Diet: Paleolithic (“Stone Age”).
30% or more protein (2:1 ratio of omega-3 to omega-6 fatty acid containing
fish, game meat, etc., 1:1 Magnesium to Calcium intake, low sodium-high
potassium) 70% complex carbohydrates (Fruits and vegetables). No grains, cereals or bovine milk.
(Helpful dietary chart can be found below)
Use of curry and Tumeric powder in foods is
encouraged.
20 minutes before
or 1 hour after meals:
800 mgs. to 1 gram: N-acetylcysteine
1 gram of Acetyl-L-carnitine
500 mgs. to 1 gram: Taurine
500 mgs. to 1.0-1.5 grams time-released Niacinamide
50 mgs. Thiamine (B1)
50-100 mgs. R-Lipoic Acid
50 mgs. Non-toxic NDGA
T4 (Thyroid) – Check with primary care physician regarding advisability of using this
(MD or DO must monitor T4 hormone level regularly). Abstract concerning
rationale for inclusion in references section.
May be of merit -
Discuss with primary healthcare provider
Velvet Deer Antler extract
(Spray or tablets). Follow product label recommendations.
Cinnamon
Extract Capsules (Counters glutamate neurotoxicity). Follow
product manufacturer recommendations. Abstract in reference section.
Drink magnesium rich “hard” water as often as possible: http://www.mgwater.com/list5.shtml . Also make green tea using this type of
water (See below)
Make and drink organic Japanese green tea 2-3 times daily http://www.o-cha.com/green-tea/Organic-Matcha-P300-Kaoru-Supreme-pr-16138.html -. This is one of the best, “Kaoru Supreme” Make using a magnesium rich water (See above for one source). NOTE: Author has no financial or other interest
in this firm or any commercial source listed in this free access regimen.
Glycerophosphocholine (GPC) – 1 or 2 capsules one (1) hour before or 2 hours
following meals.
Phosphatidylserine (PS) – 1 softgel 3 x daily or more often.
Luteolin: The scientific evidence for the benefits of luteolin
for various neurologic challenges is beginning to accrue. One luteolin-rich
source is a product called ”Lutimax” --
http://www.lutimax.com/radicals.html
Rooibos Tea
(Rich in luteolin):
http://www.dragonwater.com/search.tf/tea/rooibos_tea/?z=go_rooibos_tea&gclid=CKq9g-rR6IMCFQMZIgodqzqpLw - Organic Rooibos Tea
L-Theanine Take 1
capsule with or after each meal and snack and then 2 capsules 30 minutes
before retiring at night (Theanine appears to contribute to mood modulation
and relaxation-promotion via its ability to increase GABA and dopamine)
DIETARY
GUIDELINES -- PALEODIET
|
70 % Per Day
Chlorophyll foods
Chlorella
Sprouts
Asparagus
Beets
Carob
Cauliflower
Celery
Chard
Cucumber
Green beans
Kale
Leafy lettuce
Mustard greens
Parsnips
Prunes (bedtime)
Radishes
Spinach
String beans
Sweet potatoes
Watercress
Vegetable Juices
(Green and Yellow)
Curcumin/Curry
Cinnamon
Ginger
Ginseng
Fenugreek
Rosemary
Parsley/Cilantro
Sage
Thyme
Natural vanilla flavoring
Knox Gelatin
|
30% Per Day
(Especially the high Protein Meats & such)
Jerusalem
Artichoke
Avocado
Brussel Sprouts
Broccoli
Eggplant
Carrots
Carrot Juice (no
more than ｼ glass)
Blueberries with
plain yogurt
Red Grapes with
plain yogurt
(if not allergic)
Grape Juice
Onions, garlic
Wheat grass juice
Almonds and
filberts (not roasted or salted)
Sunflower seeds
Sesame seeds
Pumpkin seeds
Olives
Fish (be careful
of mercury content)
Cod
Haddock
Flounder
Salmon
Scrod
Tuna
Sea Bass
Bass
Sardines
Herring
Anchovies
Turkey
Chicken
Eggs
Wild Game
|
0% Per Day
Cigarettes/Cigars
Beer
Wine
Other Alcoholic
drinks
Sodas
Coffee
(Caffeinated)
Red Meat
Cloves
Foods with
Artificial colors
Preservatives
Monosodium glutamate or Vegetable
Hydrolyzed Protein
Processed foods
with increased salt or sugar
Aspartame
(Nutrasweet)
Fried Foods
Water with heavy
metals
(fluoride water
can increase the toxicity of aluminum)
Dairy
Products
|
Resources, References, Supporting Material
http://www.stemcelltherapies.org/ms.htm - This link is to a very comprehensive
article on alternative approaches to treating MS (by Dr. David A. Steenblock,
Medical Director & CEO, Steenblock Research Institute, Research & Development Laboratory, 1064
Calle Negocio #B, San Clemente,
CA. 92673)
http://www.strokedoctor.com/ - Dr. David
A. Steenblock’s medical practice website - devoted to brain repair and
rehabilitation. Many good research papers and such posted on this website.
http://author.emedicine.com/NEURO/topic286.htm
- Organophosphates, general.
http://www.safe2use.com/ca-ipm/00-11-12.htm
- The Chronic and Delayed Effects of Organophosphate (OP) Poisoning
http://www.lef.org/protocols/prtcl-156.shtml
- Heavy metals toxicity
http://www.webnat.com/
- Neurodegenerative diseases and
conditions: Causes, natural and other treatments, et cetera
Diet, supplements, abstracts, etc.
Curcumin (Diferuloylmethane) is a compound found in the Indian curry
spice, tumeric.
It has been discovered that people in India have a very low incidence
of neurological diseases and researchers have attempted to find out why this
is. They have looked at the spice, tumeric,
which was known from traditional Indian medicine as an anti-inflammatory agent effective in
wound healing. Research using curcumin, the active ingredient of tumeric, in EAE, a mouse model of multiple sclerosis, has shown
that it may be of benefit to people with MS.
Curry spice may fight multiple sclerosis
The Spice of Life - Unlocking the power of
curcumin
Piperin Home page
Curcuma longa (turmeric). Monograph.
Curcumin inhibiting of TNF-mediated
adhesion of monocytes to endothelial cells
Curcumin inhibiting of macrophage TNF-alpha
release
Effect of curcumin and capsaicin on rat
macrophages metabolism
Curcumin inhibiting differentiation in
human endothelial cells
Curcumin and oxidative activity astrocyte
cells
Regulation of IL-1 mediated MMP-9
expression in mesangial cells
Influence of piperine on curcumin in
animals and humans
Immunomodulatory activity of curcumin
|
J Nat Prod. 2002
Sep;65(9):1227-31.
|
|
Discovery of natural products from Curcuma longa
that protect cells from beta-amyloid insult: a drug discovery effort against
Alzheimer's disease.
Park SY, Kim DS.
Program for Collaborative Research in Pharmaceutical Sciences and Department
of Medicinal Chemistry and Pharmacognosy (m/c 877), College of Pharmacy,
University of Illinois at Chicago, 60612, USA.
From Curcuma longa, two novel compounds, 4' '-(3' "-methoxy-4'
"-hydroxyphenyl)-2' '-oxo-3' '-enebutanyl
3-(3'-methoxy-4'hydroxyphenyl)propenoate (calebin-A, 1) and
1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one (2), and seven
known compounds, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione
(curcumin, 3),
1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione
(demethoxycurcumin, 4), 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione
(bisdemethoxycurcumin, 5),
1-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-6-heptene-3,5-dione (6),
1,7-bis(4-hydroxyphenyl)-1-heptene-3,5-dione (7),
1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (8), and
1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one (9), were isolated
following a bioassay-guided fractionation scheme utilizing an assay to detect
protection of PC12 cells from beta-amyloid insult. Compounds 1, 3-5, and 7
were found to more effectively protect PC12 cells from betaA insult (ED(50) =
0.5-10 microg/mL) than Congo red (10) (ED(50) = 37-39 microg/mL).
PMID: 12350137
|
J Neurosci. 2001
Nov 1;21(21):8370-7.
|
|
The curry spice curcumin reduces oxidative damage
and amyloid pathology in an Alzheimer transgenic mouse.
Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM.
Departments of Medicine and Neurology, University
of California, Los
Angeles, Los Angeles,
California 90095,
USA.
Inflammation in Alzheimer's disease (AD) patients is characterized by
increased cytokines and activated microglia. Epidemiological studies suggest
reduced AD risk associates with long-term use of nonsteroidal
anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed
inflammation and plaque-related pathology in an Alzheimer transgenic APPSw
mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I can
cause gastrointestinal, liver, and renal toxicity. One alternative NSAID is
curcumin, derived from the curry spice turmeric. Curcumin has an extensive
history as a food additive and herbal medicine in India and is also a potent
polyphenolic antioxidant. To evaluate whether it could affect Alzheimer-like
pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of
dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque
pathology. Low and high doses of curcumin significantly lowered oxidized
proteins and interleukin-1beta, a proinflammatory cytokine elevated in the
brains of these mice. With low-dose but not high-dose curcumin treatment, the
astrocytic marker GFAP was reduced, and insoluble beta-amyloid (Abeta),
soluble Abeta, and plaque burden were significantly decreased by 43-50%.
However, levels of amyloid precursor (APP) in the membrane fraction were not
reduced. Microgliosis was also suppressed in neuronal layers but not adjacent
to plaques. In view of its efficacy and apparent low toxicity, this Indian
spice component shows promise for the prevention of Alzheimer's disease.
PMID: 11606625 [PubMed - indexed for MEDLINE]
|
J Immunol. 2002
Jun 15;168(12):6506-13.
|
|
Curcumin inhibits experimental allergic
encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT
pathway in T lymphocytes.
Natarajan C, Bright JJ.
Division of Neuroimmunology, Department of Neurology, Vanderbilt
University Medical
Center, Nashville, TN 37212, USA.
Experimental allergic encephalomyelitis (EAE) is a CD4(+) Th1 cell-mediated
inflammatory demyelinating autoimmune disease of the CNS that serves as an
animal model for multiple sclerosis (MS). IL-12 is a proinflammatory cytokine
that plays a crucial role in the induction of neural Ag-specific Th1
differentiation and pathogenesis of CNS demyelination in EAE and MS. Curcumin
(1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a naturally
occurring polyphenolic phytochemical isolated from the rhizome of the
medicinal plant Curcuma longa. It has profound anti-inflammatory activity and
been traditionally used to treat inflammatory disorders. In this study we
have examined the effect and mechanism of action of curcumin on the
pathogenesis of CNS demyelination in EAE. In vivo treatment of SJL/J mice
with curcumin significantly reduced the duration and clinical severity of
active immunization and adoptive transfer EAE. Curcumin inhibited EAE in
association with a decrease in IL-12 production from macrophage/microglial
cells and differentiation of neural Ag-specific Th1 cells. In vitro treatment
of activated T cells with curcumin inhibited IL-12-induced tyrosine
phosphorylation of Janus kinase 2, tyrosine kinase 2, and STAT3 and STAT4
transcription factors. The inhibition of Janus kinase-STAT pathway by
curcumin resulted in a decrease in IL-12-induced T cell proliferation and Th1
differentiation. These findings highlight the fact that curcumin inhibits EAE
by blocking IL-12 signaling in T cells and suggest its use in the treatment
of MS and other Th1 cell-mediated inflammatory diseases.
PMID: 12055272 [PubMed - indexed for MEDLINE]
NEW
ORLEANS (Reuters Health) - Preliminary
studies in rats suggest that curcumin, a compound found in the curry spice
turmeric, may block the progression of multiple sclerosis (MS).
According to researcher Dr. Chandramohan Natarajan of Vanderbilt
University in Nashville, Tennessee, rats with an MS-like illness showed
little or no signs of disease symptoms after being injected with curcumin,
while animals without the treatment went on to severe paralysis.
"We got a very good inhibition of the disease by treating with
curcumin," Natarajan told Reuters Health. He presented the findings here
Tuesday at the annual Experimental Biology 2002 conference.
No one knows what causes multiple sclerosis, in which the body's immune
system attacks the protective myelin sheath surrounding nerve fibers in the
brain and spine. Symptoms of multiple sclerosis include muscle weakness and
stiffness, balance and coordination problems, numbness and vision
disturbances.
Interest in the potential neuroprotective properties of curcumin rose
after studies found very low levels of neurological diseases such as
Alzheimer's in elderly Indian populations. Added to this were studies confirming
curcumin as a potent anti-inflammatory agent, effective in wound healing. And
just last fall, researchers at the University
of California, Los Angeles reported that curcumin appeared
to slow the progression of Alzheimer's in mice.
In their 30-day study, Natarajan and co-researcher Dr. John Bright gave
injections of 50- and 100-microgram doses of curcumin, three times per week,
to a group of mice bred to develop a disease called experimental autoimmune
encephalomyelitis (EAE)--an autoimmune condition used by researchers as a
model for multiple sclerosis because it also results in the slow erosion of
myelin. They then watched the rats for signs of MS-like neurological
impairment.
By day 15, rats who had not received curcumin developed EAE to such an
extent that they displayed complete paralysis of both hind limbs, according
to Natarajan.
In contrast, rats given the 50-microgram dose of the curry compound
showed only minor symptoms, such as a temporarily stiff tail. And rats given
the 100-microgram dose appeared completely unimpaired throughout the 30 days
of the study.
The results didn't really surprise Natarajan. "In Asian countries,
such as India, China, who are eating more spicy foods, more yellow compounds
like curcumin...there are only very, very rare reports of MS," he
pointed out. He said the doses the rats received were roughly equivalent in
human terms to those found in a typical Indian diet.
Just how curcumin might work to thwart the progression of demyelinization
remains unclear. But the Nashville
researchers believe it may interrupt the production of IL-12, a protein that
plays a key role in signaling immune cells to launch their assault on the
myelin sheath.
Natarajan stressed that "we have to do a lot of work on this,"
including examining other potential mechanisms by which curcumin slows EAE
and, potentially, MS.
The work remains preliminary, and MS patients should follow their
doctor's advice when it comes to treating the disease. Still, Natarajan said
adding a little curry to the diet couldn't hurt. "I think using this
spice in their food could be of help," he said.
http://www.iherb.com/tumeric.html
Blue Wavelength light exposure may ameliorate MS
Animal Model of Multiple Sclerosis:
・To help in research of multiple sclerosis (MS) researchers utilize an
animal model, experimental allergic encephalitis (EAE). EAE is an acute
autoimmune demyelination disease, that matches the symptomatology of MS. Guinea
pigs with EAE are reported to have a reduction of serotonin within the
central nervous system (CNS), when compared to control subjects. The
reduction of serotonin within the CNS leads to an effect on CNS serotonin
transmissions in EAE, either at the level of serotonin receptor itself, or at
the level of serotonin transmitting neurons (Scott, Cashman, and Spitler, 1982-83).
The symptoms of EAE are due to the inhibition of serotonin transmission.
In animals with EAE,
administration of L-5-hydroxytrytophan, a precursor to serotonin, reversed
the effects of impaired serotonergic transmission. Suggesting that there
might be a blockade of serotonin receptors (Scott, Cashman, and Spitler, 1982-83),
which can be overcome by the addition of a drug that increases the CNS
serotonin levels. The addition of a precursor of serotonin has such an
effect, and then the addition of antidepressant type drugs may affect
the symptoms of EAE in a positive way.・/SPAN>
http://www.cwu.edu/~chem/courses/chem388488f00/kusche/multiple/animal.htm
--------------------------------------------------------------------------------------------------------
Scientific Breakthrough
Blue Light Wavelengths Increase Serotonin
Several very recent studies, most notably research from a team headed by
Dr. George Brainard at Thomas Jefferson Medical College in Philadelphia, have
identified the specific wavelengths of blue light, 446-477 nm that are
crucial in suppressing melatonin production in humans. 1 2 3 4 As Dr. Brainard notes,
"This discovery will have an immediate impact on the therapeutic use of
light for treating winter depression and circadian disorders."
Melatonin, the neurotransmitter that helps us sleep deeply through the night,
is produced from serotonin. Suppressing melatonin production raises the
levels of serotonin in our brains. This is the key goal of therapeutic
bright light treatment. This neurological pathway entrains our
circadian rhythm to be awake during the day and sleep deeply at night.
Four cells in the human retina capture light and form the visual
system. One type, rod cells, regulates night vision. The other
three types, called cone cells, control color vision. It's known that
exposure to light at night can disrupt the body's production of melatonin,
which is produced by the pineal gland in the brain and plays a vital role in
resetting the body's daily biological clock.
Dr. Brainard and his group showed that the combined three-cone system
didn't control the biological effects of light, at least not for melatonin
regulation. But subsequent work led to the surprising discovery that a
novel receptor was responsible for the effect.
The study looked at the effects of nine different wavelengths of light,
from indigo to orange, on 72 healthy volunteers. Subjects were brought into the laboratory at midnight, when
melatonin is highest. The subjects' pupils were dilated and then they
were blindfolded for two hours. Blood samples were drawn. Next,
each person was exposed to a specific dose of photons of one light for 90
minutes, and then another blood sample was drawn. Wavelengths of
blue light had the highest potency in causing changes in melatonin levels,
he explains.
This new research indicates that there is an as yet unidentified
photopigment; most sensitive at theses wavelengths of blue light that
controls theses neurological reactions to light. As another researcher
notes, this 'provides the first direct evidence of a non-rod, non-cone
photoreceptive system in humans' - one that is activated by blue light
between 420-480 nm. 2
We are pleased to announce that this research has been incorporated into
the BlueStarTM Light Boxes. The 10 000 lux, BlueStarTM double tubes
have one side that's bright blue (446-477 nm) and one side that's bright
white 85 CRI, 5000K. Clinical use shows that the BlueStarTM Light
raises serotonin in 15-30 minutes, instead of the 1-2 hours necessary with
bright hi lux light
1
Brainard G, Hanifin J, Gresson J, et al (2001)
Action Spectrum for Melatonin Regulation in Humans: Evidence for a
Novel Circadian Photoreceptor. Neurosci (16): 6405-6412
2 Thapan K, Arendt J, Skene DJ (2001) An action spectrum for
melatonin suppression: evidence for a novel non-rod, non-cone
photoreceptor system in humans. J Physiol 535 (pt 1): 261-7
3 Wright HR, Lack LC (2001) Effect of light wavelength on
suppression and phase delay of the melatonin rhythm. Chronobiol Int
5:801-8
4 Max, M (2001) Molecular Basis of Phototransduction and
Circadian Rhythmicity, notes on current research, Dept. of
2
Physiology and Biophysics of Mount Sinai School
of Medicine.
|
NIACINAMIDE (Nerve protectant and anti-inflammatory)
|
Clin Exp
Immunol. 2003 Jan;131(1):48-52.
|
|
Nicotinamide
is a potent inhibitor of proinflammatory cytokines.
Ungerstedt JS, Blomback M, Soderstrom T.
Coagulation Research, Department of Surgical Sciences, Karolinska
Institutet, Stockholm, Sweden.
johanna.ungerstedt@ks.se
The present study investigates the modulating effects of nicotinamide on
the cytokine response to endotoxin. In an in vitro model of endotoxaemia,
human whole blood was stimulated for two hours with endotoxin at 1 ng/ml,
achieving high levels of the proinflammatory cytokines IL-1 beta, IL-6,
IL-8 and TNF alpha. When coincubating whole blood, endotoxin and the
vitamin B3 derivative nicotinamide, all four cytokines measured were
inhibited in a dose dependent manner. Inhibition was observed already at a
nicotinamide concentration of 2 mmol/l. At a concentration of 40 mmol/l,
the IL-1 beta, IL-6 and TNF alpha responses were reduced by more than 95%
and the IL-8 levels reduced by 85%. Endotoxin stimulation activates
poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair enzyme. It has been
hypothesized that the anti-inflammatory properties of nicotinamide are due
to PARP inhibition. In the present study, the endotoxin induced PARP
activation was dose dependently decreased with 4-40 mmol/l nicotinamide or
4-100 micro mol/l 6(5H) phenanthridinone, a specific PARP inhibitor. 6(5H)phenanthridinone
however, failed to inhibit the proinflammatory cytokines. Thus, the
mechanism behind the cytokine inhibition in our model seems not to be due
to PARP inhibition. In conclusion, the present study could not only confirm
previous reports of a down-regulatory effect on TNFalpha, but demonstrates that nicotinamide is a potent modulator
of several proinflammatory cytokines. These findings demonstrate that
nicotinamide has a potent immunomodulatory effect in vitro, and may have
great potential for treatment of human inflammatory disease.
PMID: 12519385 [PubMed - indexed for MEDLINE]
|
Trends Pharmacol
Sci. 2003 May;24(5):228-32.
|
|
ｷ Nicotinamide: necessary
nutrient emerges as a novel cytoprotectant for the brain.
Maiese K, Chong ZZ.
Division of Cellular and Molecular Cerebral Ischemia, Wayne
State University,
School of Medicine
Detroit, St Antoine, MI 48201, USA. kmaiese@med.wayne.edu
Although usually identified as an essential cellular nutrient for cellular
growth and maintenance, nicotinamide is under development as a novel
cytoprotectant for acute and chronic neurodegenerative disorders. Here, we
outline support for the premise that nicotinamide both prevents and
reverses neuronal and vascular cell injury. Nicotinamide fosters DNA
integrity and maintains phosphatidylserine membrane asymmetry to prevent
cellular inflammation, cellular phagocytosis and vascular thrombosis. The
downstream cellular and molecular cascades are considered vital for the
cytoprotection offered by nicotinamide. These pathways encompass the
modulation of Akt, the forkhead transcription factor FKHRL1, mitochondrial
membrane potential, caspase activities and cellular energy metabolism, but
remain independent of intracellular pH and mitogen-activated protein
kinases. As both a therapeutic agent and an
investigational tool, nicotinamide offers new therapeutic strategies for
degenerative disorders of the CNS.
PMID: 12767721
|
Mol Cell
Biochem. 1999 Mar;193(1-2):119-25.
|
|
Newly
discovered anti-inflammatory properties of the benzamides and
nicotinamides.
Pero RW, Axelsson B, Siemann D, Chaplin D, Dougherty G.
Department of Cell and Molecular Biology, University of Lund, Sweden.
Our laboratory has concentrated on the possible regulation the benzamides
and nicotinamides may have on the processes of DNA repair and apoptosis.
Recent reports have suggested that both apoptosis and inflammation are
regulated by the transcription factor NF-kappaB. We have initiated studies
regarding the hypothesis that the benzamides and nicotinamides could
inhibit the production of tumor necrosis factor alpha (TNFalpha) and the
inflammatory response as well as induce apoptosis via inhibition of
NF-kappaB. Our data have shown that nicotinamide and two N-substituted
benzamides, metoclopramide (MCA) and 3-chloroprocainamide (3-CPA), gave
dose dependent inhibition of lipopolysacharide induced TNFalpha in the
mouse within the dose range of 10-500 mg/kg. Moreover, lung edema was
prevented in the rat by 3 x 50 mg/kg doses of 3-CPA or MCA, and 100-200
microM doses of MCA could also inhibit NF-kappaB in Hela cells. Taken together these data strongly support the notion
that benzamides and nicotinamides have potent anti-inflammatory and
antitumor properties, because their primary mechanism of action is
regulated by inhibition at the gene transcription level of NF-kappaB, which
in turn inhibits TNFalpha and induces apoptosis.
PMID: 10331648 [PubMed - indexed for MEDLINE]
|
Velvet Deer Antler for Remyelination
Deer Antler is rich
in Neurotrophin-3 and IGF, which is a player in nerve remyelination.
_____________________________________________________________
|
Brain Res. 2003
May 16;972(1-2):110-8.
|
|
Neurotrophin-3
specifically increases mature oligodendrocyte population and enhances
remyelination after chemical demyelination of adult rat CNS.
Jean I, Lavialle C, Barthelaix-Pouplard A, Fressinaud C.
Cell Biology Laboratory, UPRES EA 3143, University
Hospital, 4 rue Larrey, F 49033
Angers cedex 01, France.
isabelle.jean@med.univ-angers.fr
In human central nervous system (CNS) demyelinating diseases, spontaneous
remyelination is often incomplete. Therefore, we have tested whether
neutrotrophin-3 (NT-3) accelerates CNS myelin repair after a
chemically-induced demyelination. One group of adult rats was injected in the
corpus callosum (CC) with 1 microl of 1% lysophosphatidylcholine (LPC) and 1
microl of NT-3 (1 microg/microl), and 15 days after injury (D15)
remyelination was compared to control rats (receiving 1 microl of LPC+1
microl of vehicle buffer of NT-3). The demyelinated volume decreased by 56%
in NT-3-treated rats at D15, and immunohistochemistry showed an increase in
mature MBP(+) oligodendrocytes (OL) (+66%) in treated animals (whereas less
mature (CNP(+)) OL were unchanged). Since less than 3% axons degenerate in
this model, and as astrocytic gliosis was not modified, these data suggest that
NT-3 acts directly on cells of the OL lineage to enhance remyelination in
vivo.
PMID: 12711083
|
Mol Cell Neurosci.
2002 Feb;19(2):239-49.
|
|
Neurotrophin-3-mediated regeneration and recovery of
proprioception following dorsal rhizotomy.
Ramer MS, Bishop T, Dockery P, Mobarak MS, O'Leary D, Fraher JP, Priestley
JV, McMahon SB.
CORD (Collaboration on Repair Discoveries), The University of British
Columbia, Biosciences Building, 6270 University Boulevard, Vancouver, British
Columbia V6T 1Z4, Canada.
Injured dorsal root axons fail to regenerate into the adult spinal cord,
leading to permanent sensory loss. We investigated the ability of intrathecal
neurotrophin-3 (NT3) to promote axonal regeneration across the dorsal root
entry zone (DREZ) and functional recovery in adult rats. Quantitative
electron microscopy showed robust penetration of CNS tissue by regenerating
sensory axons treated with NT3 at 1 and 2 weeks postrhizotomy. Light and
electron microscopical anterograde tracing experiments showed that these
axons reentered appropriate and ectopic laminae of the dorsal horn, where
they formed vesicle-filled synaptic buttons. Cord dorsum potential recordings
confirmed that these were functional. In behavioral studies, NT3-treated (but
not untreated or vehicle-treated) rats regained proprioception. Recovery
depended on NT3-mediated sensory regeneration: preventing regeneration by
root excision prevented recovery. NT3 treatment allows sensory axons to
overcome inhibition present at the DREZ and may thus serve to promote
functional recovery following dorsal root avulsions in humans. (C)2002
Elsevier Science (USA).
PMID: 11860276 [PubMed - indexed for MEDLINE]
In studies, Vitamin D has been found
helpful against autoimmunity
for the down-regulation of Th1 and up-regulation of Th2 cells. It has also been
shown to regulate the neurotrophins NGF (Nerve Growth Factor), NT-3
(NeuroTrophin 3) and NT-4. In addition, D3 has also been found to
promote differentiation and cell death in neuroblastoma (brain tumour) cell
lines as well as cancers in general making it a possible weapon against
tumours.
|
J Mol Endocrinol.
1997 Oct;19(2):173-82.
|
|
_Expression of neurotrophin-3 in the growing velvet
antler of the red deer Cervus elaphus.
Garcia RL, Sadighi M, Francis SM, Suttie JM, Fleming JS.
Department of Physiology and Centre for Gene Research, Otago School of
Medical Sciences, Dunedin, New Zealand.
Antlers are organs of bone which regenerate each year from the heads of male
deer. In addition to bone, support tissues such as nerves also regenerate.
Nerves must grow at up to 1 cm/day. The control of this rapid growth of
nerves is unknown. We examined the relative _expression of neurotrophin-3
(NT-3) mRNA in the different tissues of the growing antler tip and along the
epidermal/dermal layer of the antler shaft of the red deer Cervus elaphus, using
semi-quantitative reverse transcription-polymerase chain reaction.
_Expression in the tip was found to be highest in the epidermal/dermal layer
and lowest in the cartilaginous layer in all developmental stages examined.
These data correlate well with the density and pattern of innervation of
these tissues. Along the epidermal/dermal layer of the antler shaft,
_expression was highest in the segments subjacent to the tip and lowest near
the base, arguing for differences in the temporal _expression of NT-3 in
these segments. The _expression of NT-3 in cells isolated from the different
layers of 60-day antlers did not mirror that observed when whole tissues were
used and may suggest regional specificity of NT-3 _expression within antler
tissues.
PMID: 9343309 [PubMed - indexed for MEDLINE]
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J Exp Zool. 1998
May 1;281(1):36-42.
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Detection of growth factors and proto-oncogene mRNA
in the growing tip of red deer (Cervus elaphus) antler using reverse-transcriptase
polymerase chain reaction (RT-PCR).
Francis SM, Suttie JM.
AgResearch, Invermay Agricultural Centre, Mosgiel, New Zealand.
Deer antler is a unique mammalian organ that has an annual cycle of
regeneration. The antler grows very rapidly from the tip at up to 1 cm/day in
red deer for
a 90- to 120-day period. It is hypothesised that locally produced growth
factors are required to control and stimulate this growth. The tip of the
growing antler from animals whose antlers had been growing for 30, 60, or 90
days was dissected into four zones: epidermis/dermis, reserve mesenchyme,
precartilaginous, and cartilaginous. Total RNA was extracted, and the
presence of various growth factors and proto-oncogenes was detected using
RT-PCR, IGF-I, IGF-II, TGF beta 1, TGF beta 2, c-fos, c-myc, and
beta-actin were all present as single bands of the expected molecular weight
in the four zones of the antler at each stage of growth. There were higher
levels of IGF-I, TGF beta 2, and c-myc relative to beta-actin in the
epidermis/dermis layer than in the other three zones. There were no
differences in the _expression of any of the genes between the three stages
of growth. The presence of TGF beta 3 cannot be confirmed since multiple
bands were seen in all antler tissues. A single band of the expected size for
TGF alpha was seen only in the epidermal/dermal layer of the antler, with
multiple bands of different molecular weight being detected in the other
zones of the antler. This work has demonstrated the presence of multiple
growth factors in the growing deer antler and supports the hypothesis that
paracrine/autocrine stimulation is important for regulating antler growth.
PMID: 9571767
http://www.albany.net/~tjc/nt-3.html
Gene Therapy for ALS Mice and for Patients
Information for Patients: http://www.hopkinsmedicine.org/press/2003/August/030807B.htm
It's not a cure, but a novel form of
gene therapy has delayed symptoms and almost doubled life expectancy in mice
with the equivalent of Lou Gehrig's disease, a team from the Salk Institute
and Johns Hopkins reports in the Aug. 8 issue of Science.
In experiments with mice destined to
develop the condition, injection of the gene for insulin-like growth factor-1
(IGF-1) into muscles protected nerve cells, extended survival and improved
strength, say the scientists, who are planning a clinical trial they hope to
be able to begin in the next year.
The most beneficial treatment ever
seen in the mice, it is also the first to extend animals' survival when given
after symptoms develop, the researchers say. In the experimental mice and in
people with the disease, known as amyotrophic lateral sclerosis or ALS,
nerves that control muscles gradually die, leading to paralysis and death.
"ALS is a terrible disease and
patients have few treatment options today. We're very excited about
this," says Jeffrey Rothstein, M.D., Ph.D., professor of neurology and
neuroscience and director of the Packard
Center for ALS Research
at Johns Hopkins. "Even in mice, progression of the disease is so rapid
that we only test possible treatments before the mice get sick. It is amazing
that this gene therapy can slow progression even after symptoms
develop."
Gene therapies use a virus to deliver
specific genetic instructions to cells and usually have to be delivered
directly to where the gene is needed. But instead of injecting this
"adeno-associated" virus into specific nerves in the brain and
spinal cord -- a feat that is likely impossible -- researchers at the Salk
discovered and took advantage of the virus's ability to migrate from muscle
into the nerves that control them. The nerve cells then made the IGF-1
protein.
"IGF-1 protein has been used in
clinical trials, but with marginal results," said Fred H. Gage, Ph.D.,
professor of genetics at the Salk Institute. "The biggest challenge has
been to deliver the protein across the blood-brain barrier into the central
nervous system."
Studying a fluorescent version of the
adeno-associated virus, Salk research fellow Brian Kaspar discovered that it
could travel from muscles into nerves. Once in the nerves' nuclei, the cells'
machinery pumped out the glowing protein.
The virus's ability to migrate (known
as "retrograde delivery") into nerves from muscle gets the
therapeutic IGF-1 protein where it appears to be needed most -- the brain and
spinal cord. The researchers showed that when IGF-1 is only produced in
muscle, the benefit is minimal.
Key to the work is a mouse model of
ALS, developed in part at Johns Hopkins. Without any treatment, these mice,
engineered to make extra superoxide dismutase-1 (SOD-1), develop the first
symptoms of weakness at 90 days of age and succumb to the paralysis within
the next 45 days.
Injection of the IGF-1 gene therapy
into both quadriceps (upper hindlimb) muscles and into muscles between the
ribs that help control breathing maintained strength and lengthened survival.
Mice that received IGF-1 gene therapy
at 60 days of age developed symptoms 31 days later than untreated mice (i.e.,
at 121 days) and lived, on average, 40 days longer. The treated mouse that
survived the longest lived 265 days, while the longest-lived control mouse
lived just 140 days. Mice that received injections of IGF-1 gene therapy at
90 days of age lived an average of 22 days longer than their untreated
counterparts.
In addition to planning a clinical
trial, the researchers will also continue to investigate how IGF-1 protects
nerves to improve understanding of the disease and increase the therapeutic
potential of IGF-1.
About 30,000 people in the United States
have ALS, and about 5,000 new cases are diagnosed each year. Most will die
within five years of their diagnosis. While excessive SOD-1 in mice simulates
the effects of the human disease, the cause of ALS in people is not known.
The Johns Hopkins researchers were
funded by Project ALS. The Salk researchers were funded by Project ALS,
Christopher Reeve Foundation, the National Institute on Aging and the
National Institute of Neurological Diseases and Stroke.
Authors on the paper are Kaspar, Gage
and Nushin Sherkat of the Salk Institute for Biological Studies, and
Rothstein and Jeronia Llado of The Johns Hopkins University School of
Medicine.
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