The synaptic maintenance problem: membrane recycling, Ca2+ homeostasis and late onset degeneration

Molecular Neurodegeneration

Peter Robin Hiesinger¹  Ilya Bezprozvanny² 

[1] Department of Physiology, UT Southwestern Medical Center, 6001 Forest Park Road, Dallas 75390-9040, TX, USA;Laboratory of Molecular Neurodegeneration, St Petersburg State Polytechnical University, 195251, St Petersburg, Russia

关键词: Excitotoxicity;    Calcineurin;    Ataxia;    Lysosomal storage disorder;    Hereditary motor and sensory neuropathy;    Huntington’s disease;    Amyloid;    Presenilin;    Calcium;    Alzheimer’s disease;    Autophagy;    Endosome;    Neurodegeneration;   

Others  :  862265
DOI  :  10.1186/1750-1326-8-23

 received in 2013-04-11, accepted in 2013-07-05,  发布年份 2013

【 摘 要 】

Most neurons are born with the potential to live for the entire lifespan of the organism. In addition, neurons are highly polarized cells with often long axons, extensively branched dendritic trees and many synaptic contacts. Longevity together with morphological complexity results in a formidable challenge to maintain synapses healthy and functional. This challenge is often evoked to explain adult-onset degeneration in numerous neurodegenerative disorders that result from otherwise divergent causes. However, comparably little is known about the basic cell biological mechanisms that keep normal synapses alive and functional in the first place. How the basic maintenance mechanisms are related to slow adult-onset degeneration in different diseasesis largely unclear. In this review we focus on two basic and interconnected cell biological mechanisms that are required for synaptic maintenance: endomembrane recycling and calcium (Ca²⁺) homeostasis. We propose that subtle defects in these homeostatic processes can lead to late onset synaptic degeneration. Moreover, the same basic mechanisms are hijacked, impaired or overstimulated in numerous neurodegenerative disorders. Understanding the pathogenesis of these disorders requires an understanding of both the initial cause of the disease and the on-going changes in basic maintenance mechanisms. Here we discuss the mechanisms that keep synapses functional over long periods of time with the emphasis on their role in slow adult-onset neurodegeneration.

【 授权许可】

   
2013 Bezprozvanny and Hiesinger; licensee BioMed Central Ltd.

【 图 表 】

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