생화학분자생물학회

	Name: Tae Su Choi ( choitaesu@korea.ac.kr )
	2023-present	Assistant Professor, Division of Life Sciences, Korea University, South Korea
	2019-2023	Postdoctoral Researcher, University of California, San Diego, USA
	2017-2019	Assistant Research Professor, Department of Chemistry, Korea University, South Korea
	2012-2017	Ph.D., Department of Chemistry, POSTECH, South Korea

Distinctive Contribution of Two Additional Residues in Protein Aggregation of Aβ42 and Aβ40 Isoforms

Amyloid-β (Aβ) is one of the amyloidogenic intrinsically disordered proteins (IDPs) that self-assemble to protein aggregates incurring cell malfunction and cytotoxicity. While Aβ has been comprehended to regulate multiple physiological functions, such as enhancing synaptic functions, aiding in the recovery of the blood-brain barrier/brain injury, and exhibiting tumor suppression/antimicrobial activities, the hydrophobicity of the primary structure promotes pathological aggregations closely associated with the onset of Alzheimer’s Disease (AD). Aβ proteins consist of multiple isoforms with 37–43 amino acid residues that are produced by the cleavage of amyloid-β precursor protein (APP). The hydrolytic products of APP are secreted to the extracellular regions of neuronal cells. Aβ 1–42 (Aβ42) and Aβ 1–40 (Aβ40) are dominant isoforms whose significance in AD pathogenesis has been highlighted in numerous studies for understanding molecular mechanism and developing AD diagnosis and therapeutic strategies. In this review, we will focus on the differences between Aβ42 and Aβ40 in molecular mechanism of amyloid aggregations mediated by the two additional residues (Ile41 and Ala42) of Aβ42. The current comprehension of Aβ42 and Aβ40 in AD progression will be outlined with aggregation mechanisms of Aβ42 and Aβ40 and structural features of Aβ42 and Aβ40 amyloid fibrils. Furthermore, the impact of the heterogeneous distribution of Aβ isoforms during amyloid aggregations will be discussed in the system mimicking the coexistence of Aβ42 and Aβ40 in human cerebrospinal fluid (CSF) and plasma.


BMB Rep. 2024 Jun;57(6):263-272. doi: 10.5483/BMBRep.2024-0044
https://pubmed.ncbi.nlm.nih.gov/38835114/