Anavex Life Sciences Corp (AVXL)

[Biostockclub]

And, further, sokol, Rubyred:

The MTA “was always a dim hope, now gone dark” (no source cited so you can’t check it....but never mind that - it’s golden!)

Oh, but just in case you still want to know a little more about the subject, check out these very recent articles and UPCOMING presentation 10/10/18 at ECTRIMS

Be careful not to search on “oligodendrocyte precursor differentiation”
you’ll get tons of hits and end up in a non-specific blind alley.

Try “mitochondrial dysfunction” and better yet “Sigma 1 receptor agonists”
Got that?????:)

Happy researching,
Bio


LINK TO ECTRIMS 2018 OCTOBER 10, 2018 in Berlin
http://www.professionalabstracts.com/ectrims2018/iplanner/#/presentation/1121

Title Suggests S1R agonists protect oligodendroglia from death in MS patients (actually, it STATES it. And, it’s a link! Growing less dark...a little light up ahead??)

P582 - Sigma 1 receptor and melanocortin receptor agonists protect oligodendroglia from death induced by products of B cells from multiple sclerosis patients
R. Lisak1, L. Nedeelkoska1, H. Touil2, A. Bar-Or2, J. Benjamins1 1Neurology, Wayne State University School of Medicine, Detroit, MI, 2Neurology, University of Pennsylvania, Philadlephia, PA, United States
The complete abstract will be published on September 26, 2018.

“PROTECT OLIGODENDROGLIA FROM DEATH”
(No MIGHT!!!, emphasis)

Abstract will be published on Wednesday

Additionally:
This link was tweeted on Sept 18, 2018 (last Tues) following the 7th Molecular Mechanisms of Axonal Degeneration MeetIng, which was held in Scotland in August 3-6. They just tweeted the link to this pub last week.
See? Links! (With authors, sources...)


https://www.sciencedirect.com/science/article/pii/S0959438818300345



Maintenance mechanisms of circuit-integrated axons
Author links open overlay panel
VittoriaMariano124ClaudiaBagni135
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https://doi.org/10.1016/j.conb.2018.08.007
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Highlights
•
Following axonal growth and pathfinding, circuit integrated axons require local mechanisms for survival.
•
MITOCHONDRIAL HOMEOSTASIS*, axoskeletal support, and glial nurturing are crucial for the maintenance of axons.
•
Mechanisms of axonal support are impaired in neurodevelopmental and neurodegenerative diseases.
Adult, circuit-integrated neurons must be maintained and supported for the life span of their host. The attenuation of either maintenance or plasticity leads to impaired circuit function and ultimately to neurodegenerative disorders. Over the last few years, significant discoveries of molecular mechanisms were made that mediate the formation and maintenance of axons. Here, we highlight intrinsic and extrinsic mechanisms that ensure the health and survival of axons. We also briefly discuss examples of mutations associated with impaired axonal maintenance identified in specific neurological conditions. A better understanding of these mechanisms will therefore help to define targets for therapeutic interventions.

*Caps mine

Here’s what that meeting is focused on:

1st Axon Degeneration meeting in Scotland. How axons die in multiple sclerosis, motor neuron disease, Alzheimer's... Now fundraising pic.twitter.com/8i3srgzect

— Julia Edgar (@JuliaEdgar1) October 28, 2017

Julia Edgar
1st Axon Degeneration meeting in Scotland. How axons die in multiple sclerosis, motor neuron disease, Alzheimer's... Now fundraising
(*from last October)

Another Mitochondrial Repair article from 2018 linked by this same seminar discusses neuroinflammation.
https://www.ncbi.nlm.nih.gov/m/pubmed/29486771/


Mitochondrial damage and "plugging" of transport selectively in myelinated, small-diameter axons are major early events in peripheral neuroinflammation.
Sajic M, et al. J Neuroinflammation. 2018.
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Abstract
BACKGROUND: Small-diameter, myelinated axons are selectively susceptible to dysfunction in several inflammatory PNS and CNS diseases, resulting in pain and degeneration, but the mechanism is not known.
METHODS: We used in vivo confocal microscopy to compare the effects of inflammation in experimental autoimmune neuritis (EAN), a model of Guillain-Barré syndrome (GBS), on mitochondrial function and transport in large- and small-diameter axons. We have compared mitochondrial function and transport in vivo in (i) healthy axons, (ii) axons affected by experimental autoimmune neuritis, and (iii) axons in which mitochondria were focally damaged by laser induced photo-toxicity.
RESULTS: Mitochondria affected by inflammation or laser damage became depolarized, fragmented, and immobile. Importantly, the loss of functional mitochondria was accompanied by an increase in the number of mitochondria transported towards, and into, the damaged area, perhaps compensating for loss of ATP and allowing buffering of the likely excessive Ca2+ concentration. In large-diameter axons, healthy mitochondria were found to move into the damaged area bypassing the dysfunctional mitochondria, re-populating the damaged segment of the axon. However, in small-diameter axons, the depolarized mitochondria appeared to "plug" the axon, obstructing, sometimes completely, the incoming (mainly anterograde) transport of mitochondria. Over time (~?2 h), the transported, functional mitochondria accumulated at the obstruction, and the distal part of the small-diameter axons became depleted of functional mitochondria.
CONCLUSIONS: The data show that neuroinflammation, in common with photo-toxic damage, induces depolarization and fragmentation of axonal mitochondria, which remain immobile at the site of damage. The damaged, immobile mitochondria can "plug" myelinated, small-diameter axons so that successful mitochondrial transport is prevented, depleting the distal axon of functioning mitochondria. Our observations may explain the selective vulnerability of small-diameter axons to dysfunction and degeneration in a number of neurodegenerative and neuroinflammatory disorders.

Let’s keep the lights on!
Bio