1. Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia: From experimental models to neurodegenerative diseases
- Author
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Paolo Gubellini, Barbara Picconi, Massimiliano Di Filippo, Paolo Calabresi, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], and Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia'
- Subjects
MESH: Cell Death ,Huntingtin ,Parkinson's disease ,striatum ,Gene mutation ,Parkin ,Basal Ganglia ,3-nitropropionic acid ,MESH: Neurodegenerative Diseases ,MESH: Basal Ganglia ,rotenone ,0302 clinical medicine ,Basal ganglia ,MESH: Animals ,Basal Ganglia/*metabolism/physiopathology ,parkin ,Basal ganglia disease ,0303 health sciences ,Cell Death ,Neurodegenerative Diseases ,Parkinson Disease ,Parkinson Disease/metabolism ,3. Good health ,Mitochondria ,Huntington Disease ,Biochemistry ,mitochondrial fusion ,Molecular Medicine ,Huntington Disease/metabolism ,dopamine ,MESH: Mitochondria ,huntingtin ,PINK1 ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Huntington's chorea ,03 medical and health sciences ,medicine ,Neurodegenerative Diseases/*metabolism ,Animals ,Molecular Biology ,long-term potentiation ,030304 developmental biology ,Mitochondria/*metabolism ,Animal ,medicine.disease ,MESH: Huntington Disease ,Disease Models, Animal ,Disease Models ,DNAJA3 ,MESH: Disease Models, Animal ,Neuroscience ,030217 neurology & neurosurgery ,MESH: Parkinson Disease - Abstract
International audience; Mitochondrial dysfunctions have been implicated in the cellular processes underlying several neurodegenerative disorders affecting the basal ganglia. These include Huntington's chorea and Parkinson's disease, two highly debilitating motor disorders for which recent research has also involved gene mutation linked to mitochondrial deficits. Experimental models of basal ganglia diseases have been developed by using toxins able to disrupt mitochondrial function: these molecules act by selectively inhibiting mitochondrial respiratory complexes, uncoupling cellular respiration. This in turn leads to oxidative stress and energy deficit that trigger critical downstream mechanisms, ultimately resulting in neuronal vulnerability and loss. Here we review the molecular and cellular downstream effects triggered by mitochondrial dysfunction, and the different experimental models that are obtained by the administration of selective mitochondrial toxins or by the expression of mutant genes.
- Published
- 2010
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