Misfolding of synaptic molecules such as amyloid β peptide and α‐synuclein has been proposed to play a key role in the mechanisms of neurodegeneration in Alzheimer's and Parkinson's disease, respectively. Notably, the majority of patients with Alzheimer's disease also have α‐synuclein‐immunoreactive Lewy bodies, and a substantial proportion of them develop a form of parkinsonism also known as Lewy body disease, that defies conventional therapies. Thus, factors involved in the pathogenesis of Alzheimer's disease might promote the development of particularly recalcitrant forms of Lewy body disease. We have shown that the amyloid β peptide 1‐42, of Alzheimer's disease, promotes the toxic conversion of α‐synuclein and accelerates α‐synuclein‐dependent deficits in transgenic mice. Understanding the mechanisms promoting the toxic conversion of α‐synuclein is of critical importance for the design of rationale treatments for Lewy body disease and transgenic models hold the promise for the development of such novel therapies. In this context therapies aimed at: (1) reducing amyloid β peptide 1‐42 production, (2) blocking toxic α‐synuclein oligomerization (e.g., β‐synuclein, antioxidants), (3) promoting α‐synuclein protofibril degradation, and (4) protecting neurons (e.g., anti‐oxidants, neurotrophic agents) against toxic α‐synuclein aggregates might prove to be significantly useful in the treatment of Lewy body disease. We characterized β‐synuclein, the non‐amyloidogenic homologue of α‐synuclein, as an inhibitor of aggregation of α‐synuclein. Our results raise the intriguing possibility that β‐synuclein might be a natural negative regulator of α‐synuclein aggregation, and that a similar class of endogenous factors might modulate the toxic conversion of other molecules involved in neurodegeneration. Such an anti‐amyloidogenic property of β‐synuclein in combination with other treatments might also provide a novel strategy for the treatment of neurodegenerative disorders. Drug Dev. Res. 56:282–292, 2002. © 2002 Wiley‐Liss, Inc.

EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001849 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001849 | SxmlIndent | more

{{Explor lien
   |wiki=    Wicri/Sante
   |area=    ParkinsonV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     ISTEX:D42B27801C8A61B758FF8CC4A9D57A6A9F7E9E7F
   |texte=   Progress in the development of new treatments for combined Alzheimer's and Parkinson's diseases
}}