Differential involvement of caspase-6 in amyloid-β-induced fragmentation of lamin A and B

Biochemistry and Biophysics Reports

Il-Seon Park¹  Md Selim Hossain¹  Md Imamul Islam¹ 

[1] Department of Medical Sciences, Republic of Korea;

关键词: Amyloid β;    Alzheimer's disease;    Lamin;    Nuclear scaffold protease;    Caspase-6;    Phosphorylation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Amyloid-β (Aβ), a peptide implicated in Alzheimer's disease, was shown to cause specific fragmentation of lamin proteins, which was mediated by an unidentified protease named nuclear scaffold protease (NSP) independently of caspase-6. Because caspase-6 is responsible for the fragmentation process in many other damage-induced apoptosis, here we further investigated possible involvement of caspase-6 in Aβ-induced lamin fragmentation under various conditions. We found that lamin A fragment generated by NSP (named fragment b) disappeared in cells incubated with Aβ42 for prolonged periods and this product was preserved by a caspase-6 inhibitor. Furthermore, caspase-6 could remove fragment b in nuclei isolated from Aβ42-treated cells (ANU). Lamin B in ANU was fragmented by caspase-6 only after treatment with an alkaline phosphatase. The caspase-mediated fragmentation of lamin B was also achieved with nuclei isolated from cells incubated with Aβ42 plus a Cdk5 inhibitor. The results indicate that Aβ42 induces NSP-mediated fragmentation of lamin A and the following removal process of fragment b by caspase-6 and an Aβ-induced phosphorylation prevents the fragmentation of lamin B by caspase-6. The pathway leading to lamin protein fragmentation in this investigation appears to be specific for Aβ and thus the data will provide novel insights into the toxicity of the peptide.

【 授权许可】

Unknown