Pathophysiology of synuclein aggregation in Lewy body disease

Mech Ageing Dev. 2006 Feb;127(2):188-202. doi: 10.1016/j.mad.2005.09.014. Epub 2005 Nov 16.

Abstract

We provide an overview of synaptic pathology in dementia with Lewy bodies (DLB) and related neurodegenerative disorders that are characterised by intraneuronal accumulation of alpha-synuclein aggregates. The review addresses the clinico-neuropathological correlates of synaptic pathology in Lewy body disease, and concentrates on: altered alpha-synuclein metabolism, mechanisms leading to alpha-synuclein fibril formation (self-polymerisation, alpha-synuclein mutations and post-translational modifications) and how these influence the axonal transport and synaptic network in ageing and disease process. Understanding the mechanisms leading to intraneuronal alpha-synuclein accumulation are crucial for the development of novel therapies for treatment of Lewy body disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / metabolism
  • Aging / pathology
  • Axons / metabolism
  • Axons / pathology
  • Biological Transport
  • Humans
  • Lewy Body Disease / metabolism*
  • Lewy Body Disease / pathology*
  • Lewy Body Disease / therapy
  • Multiprotein Complexes / metabolism*
  • Synapses / metabolism
  • Synapses / pathology
  • alpha-Synuclein / metabolism*

Substances

  • Multiprotein Complexes
  • alpha-Synuclein