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The neurotoxicity of amphetamines: bridging drugs of abuse and neurodegenerative disorders.

Abstract：

:Amphetamine derivatives are the most commonly abused drugs. These compounds have been known for many years to induce neurotoxicity. However, recent findings have highlighted novel alterations produced by amphetamines in the central nervous system consisting of neuronal inclusions and the involvement of proteins belonging to a multi-enzymatic complex known as the ubiquitin-proteasome system. These ultrastructural and molecular changes are similar to those that occur during degenerative processes that affect the basal ganglia, and in particular Parkinson's disease, which is characterized by ubiquitin-containing neuronal inclusions in the subtantia nigra. This is recently confirmed by the occurrence of ubiquitin immunoreactive structures in the substantia nigra of humans abusing methamphetamines. In this article, we propose that the neurotoxicity of amphetamines and degenerative disorders share a number of steps in their mechanism of action involving the ubiquitin-proteasome system. The fine tuning of this ubiquitous proteolytic pathway is now being elucidated because G-protein-coupled receptors and signaling proteins such as beta-arrestin regulate access to this catalytic machinery. The identification of the ubiquitin-proteasome pathway and beta-arrestin as molecular targets of neurotoxicity is expected to provide novel therapeutic strategies both for the treatment of drug addiction and the treatment of neurodegenerative disorders.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Iacovelli L,Fulceri F,De Blasi A,Nicoletti F,Ruggieri S,Fornai F

doi

10.1016/j.expneurol.2006.02.130

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

24-31

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(06)00212-3

journal_volume

201

pub_type

杂志文章,评审

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