Open AccessChaperone signalling complexes in Alzheimer's disease
Author(s) -
Koren John,
Jinwal Umesh K.,
Lee Daniel C.,
Jones Jeffrey R.,
Shults Cody L.,
Johnson Amelia G.,
Anderson Laura J.,
Dickey Chad A.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00557.x
Subject(s) - chaperone (clinical) , co chaperone , hsp90 , protein folding , hsp70 , microbiology and biotechnology , biology , heat shock protein , proteasome , cdc37 , protein aggregation , chemical chaperone , amyloid disease , biochemistry , unfolded protein response , disease , endoplasmic reticulum , amyloid β , amyloid fibril , medicine , pathology , gene
• Introduction ‐ Chaperones: the basics ‐ Hsp90, Hsp70 and CHIP ‐ Substrate processing ‐ Client degradation versus folding ‐ Chaperone expression ‐ Small Hsps• Chaperone regulation in Alzheimer's disease ‐ Chaperone involvement in APP, presenilins and amyloid processing ‐ Chaperone regulation of the MAPT• ConclusionsAbstract Molecular chaperones and heat shock proteins (Hsp) have emerged as critical regulators of proteins associated with neurodegenerative disease pathologies. The very nature of the chaperone system, which is to maintain protein quality control, means that most nascent proteins come in contact with chaperone proteins. Thus, amyloid precursor protein (APP), members of the gamma‐secretase complex (presenilin 1 [PS1] collectively), the microtubule‐associated protein tau (MAPT) as well as a number of neuroinflammatory components are all in contact with chaperones from the moment of their production. Chaperones are often grouped together as one machine presenting abnormal or mutant proteins to the proteasome for degradation, but this is not at all the case. In fact, the chaperone family consists of more than 100 proteins in mammalian cells, and the primary role for most of these proteins is to protect clients following synthesis and during stress; only as a last resort do they facilitate protein degradation. To the best of our current knowledge, the chaperone system in eukaryotic cells revolves around the ATPase activities of Hsp70 and Hsp90, the two primary chaperone scaffolds. Other chaperones and co‐chaperones manipulate the ATPase activities of Hsp70 and Hsp90, facilitating either folding of the client or its degradation. In the case of Alzheimer's disease (AD), a number of studies have recently emerged describing the impact that these chaperones have on the proteotoxic effects of tau and amyloid‐β accumulation. Here, we present the current understandings of chaperone biology and examine the literature investigating these proteins in the context of AD.