Dual Role of Autophagy in Diseases of the Central Nervous System

Abstract

Autophagy is a vital lysosomal degradation and recycling pathway in the eukaryotic cell, responsible for maintaining an intricate balance between cell survival and cell death, necessary for neuronal survival and function. This dual role played by autophagy raises the question whether this process is a protective or a destructive pathway, the contributor of neuronal cell death or a failed attempt to repair aberrant processes? Deregulated autophagy at different steps of the pathway, whether excessive or downregulated, has been proposed to be associated with neurodegenerative disorders such as Alzheimer’s-, Huntington’s-, and Parkinson’s-disease, known for their intracellular accumulation of protein aggregates. Recent observations of impaired autophagy also appeared in psychiatric disorders such as schizophrenia and bipolar disorder suggesting an additional contribution to the pathophysiology of mental illness. Here we review the current understanding of autophagy’s role in various neuropsychiatric disorders and, hitherto, the prevailing new potential autophagy-related therapeutic strategies for their treatment.

Prolyl oligopeptidase inhibition reduces PolyQ aggregation and improves cell viability in cellular model of Huntington’s disease

“…As a background to this is the finding that mHtt aggregates are known to impair the ubiquitin‐proteasome system causing a further increase in the intracellular protein load in cells. In addition, autophagy inducers can produce beneficial effects in cell culture and animal models of HD (for review, see Ref …”

“…In addition, autophagy inducers can produce beneficial effects in cell culture and animal models of HD (for review, see Ref. 3 ). However, the potential toxicity and adverse effects of such autophagy inducers may also cause serious drawbacks that has to be taken into account.…”

The Unfolded Protein Response and Autophagy as Drug Targets in Neuropsychiatric Disorders

“…Autophagy is an evolutionarily conserved mechanism and is mediated via a complex network of over 30 proteins that are conserved across species. Post-mitotic neurons become highly dependent on autophagy for reducing their cytosolic load by clearing its components like misfolded proteins and dysfunctional organelles (Bar-Yosef et al, 2019 ). Recently, specific aspects of autophagy in different neuronal compartments have been thoroughly covered (Hill and Colon-Ramos, 2020 ), and we will mainly focus on the potential role of autophagy processes in neuropsychiatric disorders.…”

Salvianolate lyophilized injection induced autophagy against neuronal apoptosis through the Akt/mTOR pathway in Neuro-2a cells

“…Autophagy, a catabolic process, is a vital phenomenon existing in eukaryotic cells. Autophagy dysfunction is closely associated with certain disease, including nervous system diseases, immune responses, cancer and diabetes [8][9][10][11]. Accumulating evidence indicates that autophagy contributes to cerebral ischemic stroke and is involved in ischemic brain injury [12,13].…”