ADAM10 isoforms: Optimizing usage of antibodies based on protein regulation, structural features, biological activity and clinical relevance to Alzheimer's ' s disease

Author(s):Show less -

Dorta, Sabrina ; Alexandre-Silva, Vanessa ; Popolin, Cecilia Patricia ; de Sousa, Danilo Barroso ; Grigoli, Marina Mantellatto ; Pelegrini, Lucas Nogueira de Carvalho ; Manzine, Patricia Regina ; Camins, Antoni ; Marcello, Elena ; Endres, Kristina ; Cominetti, Marcia Regina

• Document type: Journal article
• Source: AGEING RESEARCH REVIEWS; v. 101, p. 18-pg., 2024-09-12.

Abstract

A Disintegrin and Metalloproteinase 10 (ADAM10) is a crucial transmembrane protein involved in diverse cellular processes, including cell adhesion, migration, and proteolysis. ADAM10's ability to cleave over 100 substrates underscores its significance in physiological and pathological contexts, particularly in Alzheimer's disease (AD). This review comprehensively examines ADAM10's multifaceted roles, highlighting its critical function in the non-amyloidogenic processing of the amyloid precursor protein (APP), which mitigates amyloid beta (A beta) production, a critical factor in AD development. We summarize the regulation of ADAM10 at multiple levels: transcriptional, translational, and post-translational, revealing the complexity and responsiveness of its expression to various cellular signals. A standardized nomenclature for ADAM10 isoforms is proposed to improve clarity and consistency in research, facilitating better comparison and replication of findings across studies. We address the challenges in detecting ADAM10 isoforms using antibodies, advocating for standardized detection protocols to resolve discrepancies in results from different biological matrices. By highlighting these issues, this review underscores the potential of ADAM10 as a biomarker for early diagnosis and a therapeutic target in AD. By consolidating current knowledge on ADAM10's regulation and function, we aim to provide insights that will guide future research and therapeutic strategies in the AD context. (AU)

• FAPESP's process: 23/00449-0 - Levels and activity of ADAM10, an Alzheimers disease serum biomarker, in different cellular compartments
• Grantee: Vanessa Alexandre da Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 23/00868-2 - Structural bases of the ADAM10 isoforms proteolytic activity
• Grantee: Sabrina Dorta de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/01863-9 - Biology and function of ADAM10 isoforms for differential diagnosis of Alzheimer's Disease by electrochemical sensors
• Grantee: Márcia Regina Cominetti
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/14673-3 - Multi-user equipment approved in grant 2021/01863-9: Real time PCR system QuantStudio qPCR
• Grantee: Márcia Regina Cominetti
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 22/15314-0 - Effects of single nucleotide polymorphisms (SNPs) on ADAM10 levels and activities in patients with dementia of Alzheimer's disease compared to cognitively healthy older adults
• Grantee: Lucas Pelegrini Nogueira de Carvalho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral