Autophagy in neurodegeneration: New insights underpinning therapy for neurological diseases

Journal of Neurochemistry
Olga CortiPhilip M Beart

Abstract

In autophagy long-lived proteins, protein aggregates or damaged organelles are engulfed by vesicles called autophagosomes prior to lysosomal degradation. Autophagy dysfunction is a hallmark of several neurodegenerative diseases in which misfolded proteins or dysfunctional mitochondria accumulate. Excessive autophagy can also exacerbate brain injury under certain conditions. In this review, we provide specific examples to illustrate the critical role played by autophagy in pathological conditions affecting the brain and discuss potential therapeutic implications. We show how a singular type of autophagy-dependent cell death termed autosis has attracted attention as a promising target for improving outcomes in perinatal asphyxia and hypoxic-ischaemic injury to the immature brain. We provide evidence that autophagy inhibition may be protective against radiotherapy-induced damage to the young brain. We describe a specialized form of macroautophagy of therapeutic relevance for motoneuron and neuromuscular diseases, known as chaperone-assisted selective autophagy, in which heat shock protein B8 is used to deliver aberrant proteins to autophagosomes. We summarize studies pinpointing mitophagy mediated by the serine/threonine kinase PI...Continue Reading

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Citations

Sep 29, 2020·Neural Regeneration Research·Kenneth Maiese
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Shuwen DengWei Lu
May 27, 2020·Journal of Neural Transmission·Elena PompiliFrancesco Fornai
Jan 5, 2021·Frontiers in Neuroscience·Xiangpeng Ren, Jiang-Fan Chen
Apr 24, 2021·Neuroscience Letters·Laura Ferraiuolo, Nicholas J Maragakis
Mar 23, 2021·Clinical and Experimental Pharmacology & Physiology·Amir AjoolabadyJun Ren
Jun 1, 2021·Autophagy·Jason P ChuaSami J Barmada
Jun 3, 2021·Biology·Katsuya IuchiHisashi Hisatomi
Jun 16, 2021·Wiener medizinische Wochenschrift·Sigrid Klotz, Ellen Gelpi
Jul 10, 2021·Autophagy·Muhammed KocakOle Pless
Aug 28, 2021·International Journal of Molecular Sciences·Ching-Chi ChangChih-Li Lin
Jul 3, 2021·Molecular Neurobiology·Tarapati RanaSimona Bungau
Apr 21, 2021·Biomolecules & Therapeutics·McNeil ValenciaSung Hoon Lee

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