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Titolo:
Mitochondrial impairment in the cerebellum of the patients with progressive supranuclear palsy
Autore:
Park, LCH; Albers, DS; Xu, H; Lindsay, JG; Beal, MF; Gibson, GE;
Indirizzi:
Cornell Univ, Weill Med Coll, Burke Med Res Inst, White Plains, NY 10605 USA Cornell Univ White Plains NY USA 10605 s Inst, White Plains, NY 10605 USA Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, White Plains, NY 10605 USA Cornell Univ White Plains NY USA 10605 urosci, White Plains, NY 10605 USA Univ Glasgow, Dept Biochem, Glasgow G12 8QQ, Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G12 8QQ ow G12 8QQ, Lanark, Scotland
Titolo Testata:
JOURNAL OF NEUROSCIENCE RESEARCH
fascicolo: 5, volume: 66, anno: 2001,
pagine: 1028 - 1034
SICI:
0360-4012(200112)66:5<1028:MIITCO>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALPHA-KETOGLUTARATE DEHYDROGENASE; POSITRON EMISSION TOMOGRAPHY; NINDS NEUROPATHOLOGIC CRITERIA; RICHARDSON-OLSZEWSKI SYNDROME; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; OXIDATIVE STRESS; NITRIC-OXIDE; RAT-BRAIN; COMPLEX;
Keywords:
alpha-ketoglutarate dehydrogenase; progressive supranuclear palsy; mitochondria; oxidative stress;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Gibson, GE Cornell Univ, Weill Med Coll, Burke Med Res Inst, 785 Mamaroneck Ave, White Plains, NY 10605 USA Cornell Univ 785 Mamaroneck Ave White Plains NY USA 10605 5 USA
Citazione:
L.C.H. Park et al., "Mitochondrial impairment in the cerebellum of the patients with progressive supranuclear palsy", J NEUROSC R, 66(5), 2001, pp. 1028-1034

Abstract

Abnormalities in energy metabolism and oxidative stress accompany many neurodegenerative diseases, including progressive supranuclear palsy (PSP). Previously, we showed decreased activities of a mitochondrial enzyme complex,alpha -ketoglutarate dehydrogenase complex (KG-DHC), and marked increases in tissue malondialdehyde levels in post-mortem superior frontal cortex from the patients with PSP. The current study demonstrates that KGDHC is also significantly diminished (-58%) in the cerebellum from patients with PSP (n= 14), compared to age-matched control brains (n = 13). In contrast to cortex, markers of oxidative stress, such as malondialdehyde, tyrosine nitration or general protein carbonyl modification, did not increase in cerebellum. Furthermore, the protein levels of the individual components of KGDHC didnot decline. The activities of two other mitochondrial enzymes were measured to determine whether the changes in KGDHC were selective. The activity of aconitase, a mitochondrial enzyme with an iron/sulfur cluster, is also significantly diminished (-50%), whereas glutamate dehydrogenase activity is unchanged. The present results suggest that the interaction of metabolic impairment and oxidative stress is region-specific in PSP brain. In cerebellum, reductions in KGDHC occur in the absence of increases in common measuresof oxidative stress, and may underlie the metabolic deficits and contribute to pathological and clinical manifestation related to the cerebellum in patients with PSP. (C) 2001 Wiley-Liss, Inc.

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Documento generato il 19/01/20 alle ore 11:41:13