Amyloid beta binds procaspase-9 to inhibit assembly of Apaf-1 apoptosome and intrinsic apoptosis pathway

作者：Sharoar Md Golam; Islam Md Imamul; Shahnawaz Md; Shin Song Yub; Park Il Seon^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2014, 1843(4): 685-693.

DOI：10.1016/j.bbamcr.2014.01.008

• Apoptosis
• Amyloid-beta
• Caspase
• Apoptosome
• Intrinsic apoptosis pathway

Apoptosis is essential in the death process induced by Amyloid-p (A beta), a major constituent of diffuse plaques found in Alzheimer%26apos;s disease patients. However, we have found that caspase activation and cell death induced by staurosporine, employed to induce the intrinsic mitochondria-dependent apoptotic pathway, were significantly reduced by 42 amino-acid A beta 42, implying that the peptide also has a negative effect on the apoptotic process. The inhibitory effect of A beta 42 on the apoptotic pathway is associated with its interaction with procaspase-9 and consequent inhibition of Apaf-1 apoptosome assembly. We detected the inhibitory effect in the early stage (%26lt;8 h) of apoptosis, but later caspase activation becomes obvious. Thus we inferred that the inhibitory process on apoptosis begins at an early stage, and the later robust activation surpasses it. We propose that the apoptotic manifestation in A beta-treated cells is a combined consequence of those anti- and pro-apoptotic processes.

• 出版日期2014-4