Small heat shock protein HspB8: its distribution in Alzheimer's disease brains and its inhibition of amyloid-beta protein aggregation and cerebrovascular amyloid-beta toxicity.

[hereditary cerebral hemorrhage with amyloidosis]

Alzheimer 's disease (AD ) is characterized by pathological lesions , such as senile plaques (SPs ) and cerebral amyloid angiopathy (CAA ), both predominantly consisting of a proteolytic cleavage product of the amyloid-beta precursor protein (APP ), the amyloid-beta peptide (Abeta ). CAA is also the major pathological lesion in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D ), caused by a mutation in the gene coding for the Abeta peptide . Several members of the small heat shock protein (sHsp ) family , such as alphaB-crystallin , Hsp 27 , Hsp 20 and HspB 2 , are associated with the pathological lesions of AD , and the direct interaction between sHsps and Abeta has been demonstrated in vitro . HspB 8 , also named Hsp 22 of H 11 , is a recently discovered member of the sHsp family , which has chaperone activity and is observed in neuronal tissue . Furthermore , HspB 8 affects protein aggregation , which has been shown by its ability to prevent formation of mutant huntingtin aggregates . The aim of this study was to investigate whether HspB 8 is associated with the pathological lesions of AD and HCHWA-D and whether there are effects of HspB 8 on Abeta aggregation and Abeta-mediated cytotoxicity . We observed the expression of HspB 8 in classic SPs in AD brains . In addition , HspB 8 was found in CAA in HCHWA-D brains , but not in AD brains . Direct interaction of HspB 8 with Abeta (1 -42 ), Abeta (1 -40 ) and Abeta (1 -40 ) with the Dutch mutation was demonstrated by surface plasmon resonance . Furthermore , co -incubation of HspB 8 with D-Abeta (1 -40 ) resulted in the complete inhibition of D-Abeta (1 -40 )-mediated death of cerebrovascular cells , likely mediated by a reduction in both the beta -sheet formation of D-Abeta (1 -40 ) and its accumulation at the cell surface . In contrast , however , with Abeta (1 -42 ), HspB 8 neither affected beta -sheet formation nor Abeta-mediated cell death . We conclude that HspB 8 might play an important role in regulating Abeta aggregation and , therefore , the development of classic SPs in AD and CAA in HCHWA-D .

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Diseases presenting "discovered member of the shsp family" symptom

hereditary cerebral hemorrhage with amyloidosis

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