Anavex Life Sciences Corp (AVXL)

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Autophagy – One way AVXL 2-73 may work.

AVXL 2-73 induces autophagy. “Based on the data presented here, the use of available Sig-1R agonists to stabilize protein homeostasis by promoting autophagy may represent an added value for such a treatment approach and strongly supports further clinical studies for prevention and treatment of neurodegeneration.” https://www.mdpi.com/2073-4409/8/3/211/htm.

Autophagy fights disease through cellular self-digestion

''Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.''

https://www.nature.com/articles/nature06639

Chaperones in autophagy

Author links open overlay panelSusmitaKaushikAna MariaCuervo
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https://doi.org/10.1016/j.phrs.2012.10.002Get rights and content

Abstract

Cells continuously turn over proteins through cycles of synthesis and degradation in order to maintain a functional proteome and to exert a tight control in the levels of regulatory proteins. Selective degradation of proteins was initially thought to be an exclusive function of the ubiquitin–proteasome system, however, over the years, the contribution of lysosomes to this selective degradation, through the process of autophagy, has become consolidated. In this context, molecular chaperones, classically associated with protein folding, unfolding and assembling have been revealed as important modulators of selectivity during the autophagic process. Here, we review this relatively new role of chaperones in mediating selective autophagy and comment on how alterations of this function can lead to human pathologies associated to proteotoxicity.

https://www.sciencedirect.com/science/article/abs/pii/S1043661812001880

ANAVEX®2-73 activates the Sigma-1 receptor (S1R) protein, which serves as a molecular chaperone and functional modulator involved in restoring homeostasis.
See: https://www.globenewswire.com/news-release/2019/03/11/1751068/0/en/Anavex-Life-Sciences-Reaches-50-Enrollment-Threshold-in-ANAVEX-2-73-Parkinson-s-Disease-Dementia-PDD-Phase-2-Study-Ahead-of-Schedule.html

Chemical Inducers of Autophagy That Enhance the Clearance of Mutant Proteins in Neurodegenerative Diseases*

Abstract

Many of the neurodegenerative diseases that afflict people are caused by intracytoplasmic aggregate-prone proteins. These include Parkinson disease, tauopathies, and polyglutamine expansion diseases such as Huntington disease. In Mendelian forms of these diseases, the mutations generally confer toxic novel functions on the relevant proteins. Thus, one potential strategy for dealing with these mutant proteins is to enhance their degradation. This can be achieved by up-regulating macroautophagy, which we will henceforth call autophagy. In this minireview, we will consider the reasons why autophagy up-regulation may be a powerful strategy for these diseases. In addition, we will consider some of the drugs and associated signaling pathways that can be used to induce autophagy with these therapeutic aims in mind.

Intracellular protein misfolding and aggregation are features of many late-onset neurodegenerative diseases called proteinopathies. These include Alzheimer disease, Parkinson disease, tauopathies, and polyQ3 expansion diseases such as HD and various SCAs such as SCA3 (1, 2). Currently, there are no effective strategies to slow or prevent the neurodegeneration resulting from these diseases in humans.

https://www.ncbi.nlm.nih.gov/pubmed/20147746