TY - JOUR
T1 - Protein misfolding in Alzheimer's and Parkinson's disease
T2 - Genetics and molecular mechanisms
AU - Forloni, Gianluigi
AU - Terreni, Liana
AU - Bertani, Ilaria
AU - Fogliarino, Sergio
AU - Invernizzi, Roberto
AU - Assini, Andrea
AU - Ribizzi, Giuseppe
AU - Negro, Alessandro
AU - Calabrese, Elena
AU - Volonté, Maria Antonietta
AU - Mariani, Claudio
AU - Franceschi, Massimo
AU - Tabaton, Massimo
AU - Bertoli, Alessandro
PY - 2002/9
Y1 - 2002/9
N2 - The accumulation of altered proteins is a common pathogenic mechanism in several neurodegenerative disorders. A causal role of protein aggregation was originally proposed in Alzheimer's disease (AD) where extracellular deposition of β-amyloid (Aβ) is the main neuropathological feature. It is now believed that intracellular deposition of aggregated proteins may be relevant in Parkinson's disease (PD), amyotrophic lateral sclerosis and polyglutamine disorders. An impairment of ubiquitin-proteasome system (UPS) appears directly involved in these disorders. We reviewed the results on the role of protein misfolding in AD and PD and the influence of mutations associated with these diseases on the expression of amyloidogenic proteins. Results of genetic screening of familial cases of AD and PD are summarized. In the familial AD population (70 subjects) we found several mutations of the presenilin 1 (PS1) gene with a frequency of 12.8% and one mutation in the gene encoding the protein precursor of amyloid (APP) (1.4%). One mutation of Parkin in the homozygous form and two in the heterozygous form were identified in our PD population. We also reported data obtained with synthetic peptides and other experimental models, for evaluation of the pathogenic role of mutations in terms of protein misfolding.
AB - The accumulation of altered proteins is a common pathogenic mechanism in several neurodegenerative disorders. A causal role of protein aggregation was originally proposed in Alzheimer's disease (AD) where extracellular deposition of β-amyloid (Aβ) is the main neuropathological feature. It is now believed that intracellular deposition of aggregated proteins may be relevant in Parkinson's disease (PD), amyotrophic lateral sclerosis and polyglutamine disorders. An impairment of ubiquitin-proteasome system (UPS) appears directly involved in these disorders. We reviewed the results on the role of protein misfolding in AD and PD and the influence of mutations associated with these diseases on the expression of amyloidogenic proteins. Results of genetic screening of familial cases of AD and PD are summarized. In the familial AD population (70 subjects) we found several mutations of the presenilin 1 (PS1) gene with a frequency of 12.8% and one mutation in the gene encoding the protein precursor of amyloid (APP) (1.4%). One mutation of Parkin in the homozygous form and two in the heterozygous form were identified in our PD population. We also reported data obtained with synthetic peptides and other experimental models, for evaluation of the pathogenic role of mutations in terms of protein misfolding.
KW - Amyloid
KW - Parkin ubiquitin-proteasome system (UPS)
KW - Presenilins
KW - Synuclein
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U2 - 10.1016/S0197-4580(02)00076-3
DO - 10.1016/S0197-4580(02)00076-3
M3 - Article
C2 - 12392798
AN - SCOPUS:0036752519
VL - 23
SP - 957
EP - 976
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 5
ER -