Synaptic protein alterations in Parkinson's disease.
Alterations occur within distal neuronal compartments, including axons and synapses, during the course of neurodegenerative diseases such as Parkinson's disease (PD). These changes could hold important implications for the functioning of neural networks, especially since research studies have shown a loss of dendritic spines locating to medium spiny projection neurons and impaired axonal transport in PD-affected brains. However, despite ever-increasing awareness of the vulnerability of synapses and axons, inadequate understanding of the independent mechanisms regulating non-somatic neurodegeneration prevails. This has resulted in limited therapeutic strategies capable of targeting these distinct cellular compartments. Deregulated protein synthesis, folding and degrading proteins, and protein quality-control systems have repeatedly been linked with morphological and functional alterations of synapses in the PD-affected brains. Here, we review current understanding concerning the proteins involved in structural and functional changes that affect synaptic contact-points in PD. The collection of studies discussed emphasizes the need for developing therapeutics aimed at deregulated protein synthesis and degradation pathways operating at axonal and dendritic synapses for preserving "normal" circuitry and function, for as long as possible.
Institute for Ageing and Health, Department of Neurology, The University of Newcastle, Newcastle-Upon-Tyne, UK. ilse-sanet.pienaar@ncl.ac.uk
Ilse S
IS
Pienaar
David
D
Burn
Christopher
C
Morris
David
D
Dexter
D000818:Animals; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D013570:Synaptic Membranes / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission / Q000502:physiology; D051844:alpha-Synuclein / Q000378:metabolism / Q000502:physiology
D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein