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

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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

• Tipo de documento: Artigo Científico
• Fonte: AGEING RESEARCH REVIEWS; v. 101, p. 18-pg., 2024-09-12.

Resumo

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)

• Processo FAPESP: 23/00449-0 - Níveis e atividade da ADAM10, um biomarcador sérico da doença de Alzheimer, em diferentes compartimentos celulares
• Beneficiário: Vanessa Alexandre da Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 23/00868-2 - Bases estruturais da atividade proteolítica de isoformas da ADAM10
• Beneficiário: Sabrina Dorta de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 21/01863-9 - Biologia e função de isoformas da ADAM10 para diagnóstico diferencial da Doença de Alzheimer por sensores eletroquímicos
• Beneficiário: Márcia Regina Cominetti
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 21/14673-3 - EMU concedido no processo 2021/01863-9: Sistema de PCR em tempo real QuantStudio qPCR
• Beneficiário: Márcia Regina Cominetti
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 22/15314-0 - Efeitos de polimorfismos de nucleotídeo único (SNPs) nos níveis e atividades da ADAM10 em pacientes com demência da doença de Alzheimer em comparação com idosos cognitivamente saudáveis
• Beneficiário: Lucas Pelegrini Nogueira de Carvalho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado