ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker

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Regina Manzine, Patricia ^{[1, 2]} ; Ettcheto, Miren ^{[3, 2, 4, 5]} ; Cano, Amanda ^{[3, 6, 7]} ; Busquets, Oriol ^{[3, 2, 4, 5]} ; Marcello, Elena ^[8] ; Pelucchi, Silvia ^{[8, 9]} ; Di Luca, Monica ^[8] ; Endres, Kristina ^[10] ; Olloquequi, Jordi ^[11] ; Camins, Antoni ^{[3, 2, 4]} ; Cominetti, Marcia Regina ^[1]

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^[1] Univ Fed Sao Carlos, Dept Gerontol, Sao Carlos, SP - Brazil

^[2] Univ Barcelona, Fac Farm & Ciencies Alimentacio, Dept Farmacol Toxicol & Quim Terapeut, Barcelona - Spain

^[3] Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid 28031 - Spain

^[4] Univ Barcelona, Inst Neurociencies, Barcelona - Spain

^[5] Univ Rovira & Virgili, Unitats Bioquim & Farmacol, Fac Med & Ciencies Salut, Tarragona - Spain

^[6] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharm Pharmaceut Technol & Phys Chem, Barcelona - Spain

^[7] Inst Nanosci & Nanotechnol IN2UB, Barcelona - Spain

^[8] Univ Milan, Dept Pharmacol & Biomol Sci, Milan - Italy

^[9] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Florence - Italy

^[10] Johannes Gutenberg Univ Mainz, Univ Med Ctr Johannes Gutenberg, Dept Psychiat & Psychotherapy, Mainz - Germany

^[11] Univ Autonoma Chile, Fac Ciencias Salud, Inst Ciencias Biomed, Talca - Chile

• Tipo de documento: Artigo de Revisão
• Fonte: BIOMEDICINE & PHARMACOTHERAPY; v. 113, MAY 2019.
• Citações Web of Science: 2

Resumo

Alzheimer's disease (AD) represents a global burden in the economics of healthcare systems. Amyloid-beta (A beta) peptides are formed by amyloid-beta precursor protein (A beta PP) cleavage, which can be processed by two pathways. The cleavage by the alpha-secretase A Disintegrin And Metalloprotease 10 (ADAM10) releases the soluble portion (sA beta PP alpha) and prevents senile plaques. This pathway remains largely unknown and ignored, mainly regarding pharmacological approaches that may act via different signaling cascades and thus stimulate non-amyloidogenic cleavage through ADAM10. This review emphasizes the effects of natural compounds on ADAM10 modulation, which eventuates in a neuroprotective mechanism. Moreover, ADAM10 as an AD biomarker is revised. New treatments and preventive interventions targeting ADAM10 regulation for AD are necessary, considering the wide variety of ADAM10 substrates. (AU)

• Processo FAPESP: 17/13224-5 - Estudo da via JNK1 como alvo seletivo para o tratamento de transtorno metabólico cognitivo: análise da proteína ADAM10
• Beneficiário: Patricia Regina Manzine Moralles
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 15/24940-8 - Avaliação da eficácia de mudanças estruturais do [10]-gingerol em combinação com o quimioterápico doxorubicina para o tratamento de câncer de mama: estudos in vitro e in vivo
• Beneficiário: Márcia Regina Cominetti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/26084-1 - Avaliação da ADAM10 plaquetária em demências não-Alzheimer
• Beneficiário: Patricia Regina Manzine Moralles
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado