Effect of amyloids on the vesicular machinery: implications for somatic neurotransmission.

Abstract

Certain neurodegenerative diseases are thought to be initiated by the aggregation of amyloidogenic proteins. However, the mechanism underlying toxicity remains obscure. Most of the suggested mechanisms are generic in nature and do not directly explain the neuron-type specific lesions observed in many of these diseases. Some recent reports suggest that the toxic aggregates impair the synaptic vesicular machinery. This may lead to an understanding of the neuron-type specificity observed in these diseases. A disruption of the vesicular machinery can also be deleterious for extra-synaptic, especially somatic, neurotransmission (common in serotonergic and dopaminergic systems which are specifically affected in Alzheimer's disease (AD) and Parkinson's disease (PD), respectively), though this relationship has remained unexplored. In this review, we discuss amyloid-induced damage to the neurotransmitter vesicular machinery, with an eye on the possible implications for somatic exocytosis. We argue that the larger size of the system, and the availability of multi-photon microscopy techniques for directly visualizing monoamines, make the somatic exocytosis machinery a more tractable model for understanding the effect of amyloids on all types of vesicular neurotransmission. Indeed, exploring this neglected connection may not just be important, it may be a more fruitful route for understanding AD and PD.

• Authors: Anand Kant Das, Rucha Pandit, Sudipta Maiti
• Journal: Philosophical transactions of the Royal Society of London. Series B, Biological sciences (Philos Trans R Soc Lond B Biol Sci) Vol. 370 Issue 1672 (Jul 05 2015) ISSN: 1471-2970 [Electronic] England
• PMID: 26009766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Chemical References

• Amyloid

Topics

• Amyloid (toxicity)
• Cell Body (metabolism)
• Exocytosis (physiology)
• Humans
• Neurodegenerative Diseases (physiopathology)
• Neurons (cytology, metabolism)
• Synaptic Transmission (drug effects, physiology)
• Synaptic Vesicles (drug effects)