The multiple mechanisms of amyloid deposition: the role of parkin.
Amyloid deposition is one of the central neuropathological abnormalities in Alzheimer's disease (AD) but it also takes places in many neurodegenerative diseases such as prionic disorders, Huntington's disease (HD) and others. Up to very recently amyloid formation was considered a very slow process of deposition of an abnormal protein due to genetic abnormalities or post-translational modification of the deposited protein. Recent data suggest that the process of amyloidogenesis may be much more rapid in many cases and due to multiple mechanisms. We have found a mouse model of progressive neurodegeneration that resemble motor, behavioral and pathological hallmarks of parkinsonism and tauopathies, but surprisingly, also present amyloid deposits in brain and peripheral organs. Here we review some of these recent works which may provide new insight into the process of formation of amyloid and, perhaps, new ideas for its treatment.
Mena
Maria A
MA
Department of Neurobiology, Hospital Ramón y Cajal, and CIBERNED, Madrid, Spain.
Rodríguez-Navarro
José A
JA
de Yébenes
Justo García
JG
D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D006651:Histocytochemistry; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*
D000682:Amyloid; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D046988:Proteasome Endopeptidase Complex