Mini-Review Article

An Update on Autophagy as a Target in the Treatment of Alzheimer’s Disease

Author(s): Parnika Mohan Sose, Gaurav Mahesh Doshi and Pravin Popatrao Kale*

Volume 24, Issue 7, 2023

Published on: 22 May, 2023

Page: [547 - 567] Pages: 21

DOI: 10.2174/1389450124666230417104325

Price: $65


Proteostasis is crucial for the maintenance and proper operation of cells. Under typical circumstances, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway are used to clean out undesired, damaged, misfolded, or aggregated proteins. Any dysregulation in the above-mentioned pathways leads to neurodegeneration. One of the most renowned neurodegenerative disorders is AD. This condition is more prevalent in senior people and is frequently linked to dementia, progressive memory loss, and cognitive function decline, which further contributes to cholinergic neuron degradation and synaptic plasticity loss. Extracellular accumulation of amyloid beta plaques and the intraneuronal deposition of misfolded neurofibrillary tangles are two prime pathological reasons for AD. At present, there is no treatment for AD. All that remains available is the symptomatic treatment of this disease. Autophagy is the major mechanism by which the cells degrade the protein aggregates. Deposited immature autophagic vacuoles (AVs) in AD brains suggest interruption of a person's normal autophagy process. This review has briefly covered various forms and mechanisms of autophagy. Furthermore, the discussion in the article is supported by different ways and mechanisms via which autophagy can be stimulated in a beneficial way and can emerge as a novel target in the treatment of various metabolic CNS related disorders. In the current review article, the mTOR-dependent ones are PI3K/Akt/TSC/mTOR, AMPK/TSC/mTOR, and Rag/mTOR pathways and mTOR-independent ones which include Ca2+/calpain, inositol-dependent, cAMP/EPAC/PLC, and JNK1/Beclin-1/PI3K pathways have been discussed in details. The article sheds light on drugs which are validated with details in tabular form from recent updates in clinical trials.

Keywords: AD, autophagy, β plaques, neurofibrillary tangles, aging and alzheimer’s, mTORC1 inhibitors.

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