The cell biology of alpha-synuclein: a sticky problem?

Abstract:

:Parkinson's disease (PD) is the most common neurodegenerative motor disorder, marked by chronic progressive loss of neurons in the substantia nigra, thereby damaging purposeful control of movement. For decades, it was believed that PD was caused solely by environmental causes. However, the discovery of genetic factors involved in PD has revolutionized our attempts to understand the disease's pathology. PD now appears to be more polygenetic than previously thought and is most likely caused by a complex interaction of genetic risks and environmental exposures. The first gene found to be mutated in PD encodes for the presynaptic protein alpha-synuclein, which is also a major component of Lewy bodies and Lewy neurites, the neuropathological hallmarks of the disease. While these findings provide a classic example of how rare genetic mutations in disease can point to important pathways in idiopathic disease pathologies, much of the study of alpha-synuclein has focused on understanding how this protein undergoes the transition from an unfolded monomer to amorphous aggregates or Lewy body-like filaments rather than addressing what its fundamental function might be. Since alterations in synuclein function may predispose to the disease pathology of PD, regardless of the presence of genetic mutations, a more thorough understanding of the cellular regulation and function of alpha-synuclein may be of crucial importance to our understanding of this degenerating disorder.

journal_name

Neuromolecular Med

journal_title

Neuromolecular medicine

authors

Cole NB,Murphy DD

doi

10.1385/NMM:1:2:95

keywords:

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

95-109

issue

2

eissn

1535-1084

issn

1559-1174

pii

NMM:1:2:95

journal_volume

1

pub_type

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