TY - JOUR
T1 - Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia
T2 - From experimental models to neurodegenerative diseases
AU - Gubellini, Paolo
AU - Picconi, Barbara
AU - Di Filippo, Massimiliano
AU - Calabresi, Paolo
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - 3-nitropropionic acid
KW - Dopamine
KW - Huntingtin
KW - Huntington's chorea
KW - Long-term potentiation
KW - Parkin
KW - Parkinson's disease
KW - PINK1
KW - Rotenone
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=71949115249&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71949115249&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2009.08.001
DO - 10.1016/j.bbadis.2009.08.001
M3 - Article
C2 - 19683569
AN - SCOPUS:71949115249
VL - 1802
SP - 151
EP - 161
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 1
ER -