Mitochondrial Toxins in Basal Ganglia Disorders: From Animal Models to Therapeutic Strategies

Author(s): P. Bonsi, D. Cuomo, G. Martella, G. Sciamanna, M. Tolu, P. Calabresi, G. Bernardi, A. Pisani

Journal Name: Current Neuropharmacology

Volume 4 , Issue 1 , 2006

Become EABM
Become Reviewer
Call for Editor


Current knowledge of the pathogenesis of basal ganglia disorders, such as Huntingtons disease (HD) and Parkinsons disease (PD) appoints a central role to a dysfunction in mitochondrial metabolism. The development of animal models, based upon the use of mitochondrial toxins has been successfully introduced to reproduce human disease, leading to important acquisitions. Most notably, experimental evidence supports the existence, within basal ganglia, of a peculiar regional vulnerability to distinct mitochondrial toxins. MPTP and rotenone, both selective inhibitors of mitochondrial complex I have been extensively used to mimic PD. Accordingly, in human PD, a specific dysfunction of complex I activity was found in vulnerable dopaminergic neurons of the substantia nigra. Conversely, in HD a selective impairment of mitochondrial succinate dehydrogenase, key enzyme in complex II activity was found in medium spiny neurons of the caudate-putamen. The relevance of such finding is further demonstrated by the evidence that toxins able to primarily target mitochondrial complex II, such as malonic acid and 3-nitropropionic acid (3-NP), strikingly reproduce the main phenotypic and pathological features of HD. Despite the advances obtained from these experimental models, a deeper understanding of the molecular and cellular mechanisms underlying such neuronal vulnerability is lacking. The present review provides a brief survey of currently utilized animal models of mitochondrial intoxication, in attempt to address the cellular mechanisms triggered by energy metabolism failure and to identify potential therapeutic targets.

Keywords: Striatum, vulnerability, Parkinson's disease, Huntington's disease, progressive supranuclear palsy

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2006
Page: [69 - 75]
Pages: 7
DOI: 10.2174/157015906775203039
Price: $65

Article Metrics

PDF: 43