Non-specific peroxidase activity and catalase-inhibitory behavior of fibrillar aggregates after interaction with heme: relevance to the etiology of amyloid-related neurodegenerative disorders using the experimental-based evidences

作者：Khodarahmi Reza^*; Hossein pour Zahra; Ghobadi Sirous; Mansouri Kamran; Mostafaie Ali; Yari Khirollah; Ghadami Seyyed Abolghasem

来源：Journal of the Iranian Chemical Society, 2012, 9(6): 939-950.

DOI：10.1007/s13738-012-0111-6

• Amyloid aggregation
• Toxicity
• Heme
• Peroxidase
• alpha-Crystallin
• alpha-Chymotrypsin

The exact mechanism of cell death in neurodegenerative diseases remains obscure, but the aberrant assembly of proteins into fibrillar aggregates is accused to be the primary cause of pathogenesis. Furthermore, the structural determinants of protein fibrils that are responsible for cell dysfunction are not yet clear. In the present study, using alpha-crystallin-/alpha-chymotrypsin-based experimental systems, we reported non-specific peroxidase behavior of "heme-amyloid fibril" complex using DNA, serotonin and DOPA as potential substrates. Also, amyloid-mediated inhibition of catalase activity was documented. More importantly, we suggested that uncontrollable peroxidase activity may be involved in neurodegenerative cell toxicity via several independent (mechanistic) routes. According to the results and literature, it is reasonable to assume that oxidative stress plays at least partially a causative rather than merely bystander role in the neurofibrillary pathology in AD/PD in vivo. Since the consequence of heme-amyloid interaction has yet to be identified, additional in vitro/in vivo data on it may help us to manage amyloid aggregation processes and postpone/attenuate the onset/extent of irreversible part of neurodegenerative pathogenesis.

• 出版日期2012-12