|題目：||「 The Role of Iron in the α-Synuclein Pathology of Parkinson's Disease 」|
|演者：||University Wurzburg, Medical School Clinical Neurochemistry，Dept. of Psychiatry, Psychosomatics and Psychotherapy
Professor Peter Franz Riederer
|場所：||生涯教育研修センター 1号館 9階 901講義室|
|座長：||太田 明 先生|
「 The Role of Iron in the α-Synuclein Pathology of Parkinson's Disease 」P. Riederer, J. Sian-Hulsmann
The etiology of idiopathic Parkinson's Disease (PD) largely remains an enigma.
Pathological mechanisms include oxidative (and nitrative) stress, inflammation,excitotoxicity, mitochondrial dysfunction, altered proteolysis and finally apoptoticinduced cell death. Iron mediated cellular destruction is mediated primarily viareactive oxygen or/and nitrogen species induced oxidative stress (Fenton reaction).
Interestingly both pro-oxidants and antioxidants are present in Lewy bodies (LB).
Thus they are primary events and there before LB are build up, aggregate and grow.
Indeed, redox reactive iron is also present in LB. It may execute a dual role, one inneuronal death and secondly in LB production.
Increased free (labile) iron and OS have been shown to change the α-helicalstructure of α-synuclein (α-syn) to the beta-sheet structure facilitating generation of protofibrils and oligomerization.
α-Syn aggregates react then with aldehydes to "advanced glycation endproducts"for which iron plays a promoter role.
Additionally,oxidative stress may impair the ubiquitin proteasome system (UPS), thus accelerating the degenerative process, since the UPS is involved in removal of misfolded proteins such as α-syn aggregates.This pathway probably ascribes the protein aggregation associated with lipid peroxidation.