Neurotrophic Factors

Yukiharu Hadeishi YHADEISH at biomed.med.yale.edu
Thu Apr 7 20:00:37 EST 1994

sfm at manduca.neurobio.arizona.edu (Stephen Matheson) wrote:
>From article <2np6m8$8aa at s.ms.uky.edu>,
>by Steven W. Barger, Ph.D., posting from the account of
>mpm at seqanal.mi.uky.edu (Mark Mattson):
>> RSTETTA at DELPHI.COM (rstetta at news.delphi.com) wrote:
>> : Looking for info on what Nuerotrophic Factors consist of,
>> : and what effects them.
>> : There is a form of muscular dystrophy, spinal muscle atrophy,
>> : in which the motor nuerons are affected, weaken over time.
>> : It is similiar to ALS (amyotrophic lateral sclerosis) but
>> : progresses at a much slower rate.
>> The prototype is nerve growth factor (NGF), now recognized as a member of
>> a family of related peptides termed "neurotrophins" which all support the
>> health and/or growth of neurons.  Different family members seem to be
>> important for different types of neurons, but (as far as I know) none of
>> these has been shown to be trophic for the motor neurons which are lost
>> in ALS.  These cells may be more dependent on other factors produced by the
>> muscles they innervate.
>In fact, there is a young but rich literature indicating that at least one
>of the neurotrophins (brain-derived neurotrophic factor, or BDNF) has a
>profound trophic influence on exactly the motor neurons in question.

[deletia outlining instances wherein BDNF rescues cells]

>Here is an excerpt from the abstract [of a 20 May 1993 Nature article,
>Vol. 363:  266 - 70) :  "...picomolar concentrations of ...
>brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-5,
>can prevent the death of cultured embryonic rat spinal motor neurons.
>Furthermore, messenger RNA coding for neurotrophins is present at
>appropriate stages in spinal cord and limb bud, and mRNA for their
>receptors is found in motor neurons.  These neurotrophins may
>therefore be physiological motor neuron growth factors."
>The significance of these studies in terms of treatment of ALS
>and/or other degenerative disorders of motor neurons is mentioned
>in every article.

Isn't there also evidence that CNTF (Ciliary Neurotrophic Factor) also rescues
motor neurons?  I realize that CNTF does not belong to the same family of
neurotrophins as does NGF, BDNF, NT-3 or NT-4/5 and that it does not act via
any of the Trk's or by p75, the low-affinity neurotrophin receptor, but it is
known to have neurotrophic effect, isn't that right?  If I am not mistaken, I
think CNTF is found in high concentrations in Schwann cells, the glial cells
that surround peripheral axons, so that the neurotrophin is released on axonal
damage.  Aren't they also considering CNTF in the treatment of ALS?

Being more of an intracellular signal transduction kinda guy myself, I know
more about the signaling pathway of CNTF than I know what it's good for.  ;-)
If you want to know like *I* wanted to know, check out A Bonni et al. in last
December's _Science 262_: 1575-9.  That's the December 3rd issue, if you happen
to subscribe.  Or if your library hasn't gotten around to binding that week's
issue.  It seems to signal through the JAK-STAT pathway...

Anyway, I hope this helps.  If noone else than Regeneron...  ;-)

  -- yh.

Yukiharu "Yuki" Hadeishi   -   <yhadeish at biomed.med.yale.edu>
The Interdepartmental Neuroscience Program will have
absolutely nothing to do with any of my opinions...

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