Title

Clearing The Brain'S Cobwebs: The Role Of Autophagy In Neuroprotection

Keywords

Aggregates; Apoptosis; Autophagy; Cell death; Mitochondria; Neurodegeneration; Neurons; Survival

Abstract

Protein aggregates or inclusion bodies are common hallmarks of age-related neurodegenerative disorders. Why these agiplates form remains unclear. Equally debated is whether they are toxic, protective, or simple by-products. Increasing evidence, however, supports the notion that in general aggregates confer toxicity and disturb neuronal function by hampering axonal transport, synaptic integrity, transcriptional regulation, and mitochondrial function. Thus, neuroscientists in search of effective treatments to slow neural loss during neurodegeneration have long been interested in finding new ways to clear inclusion bodies. Intriguingly, two studies using conditional neuron-specific gene ablations of autophagy regulators in mice revealed that autophagy loss elicits inclusion body formation and a neurodegenerative cascade. Such studies indicate autophagy may be a built-in defense mechanism to clear the nervous system of inclusion bodies. This new finding has implications for our understanding of aging and neurodegeneration and the development of new therapies. First, we discuss the pathways underlying autophagy and its controversial role in cell death and survival regulation. We then discuss the physiological role of autophagy in the aging process of the nervous system. In the final portion of this review, we discuss the therapeutic promise of inducing autophagy and the potential side effects of such treatments. © 2008 Bentham Science Publishers Ltd.

Publication Date

6-1-2008

Publication Title

Current Neuropharmacology

Volume

6

Issue

2

Number of Pages

97-101

Document Type

Review

Personal Identifier

scopus

DOI Link

https://doi.org/10.2174/157015908784533897

Socpus ID

47749142489 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/47749142489

This document is currently not available here.

Share

COinS