The Implication of the Brain Insulin Receptor in Late Onset Alzheimer's Disease Dementia

Autor(es):Mostrar menos -

Folch, Jaume ^{[1, 2]} ; Ettcheto, Miren ^{[1, 2, 3, 4]} ; Busquets, Oriol ^{[1, 2, 3, 4]} ; Sanchez-Lopez, Elena ^{[2, 5, 6]} ; Castro-Torres, Ruben D. ^{[2, 7, 3, 4, 8]} ; Verdaguer, Ester ^{[2, 4, 8]} ; Manzine, Patricia R. ^{[3, 9]} ; Rabiei Poor, Saghar ^[3] ; Luisa Garcia, Maria ^{[5, 6]} ; Olloquequi, Jordi ^[10] ; Beas-Zarate, Carlos ^[7] ; Auladell, Carme ^{[2, 4, 8]} ; Camins, Antoni ^{[2, 3, 4]}

Afiliação do(s) autor(es)

^[1] Univ Rovira & Virgili, Fac Med & Ciencies Salut, Dept Bioquim & Biotecnol, E-43201 Reus - Spain

^[2] Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid 28031 - Spain

^[3] Univ Barcelona, Fac Farm & Ciencies Alimentacio, Dept Farmacol Toxicol & Quim Terapeut, Av Joan XXIII 27-31, E-08028 Barcelona - Spain

^[4] Univ Barcelona, Inst Neurociencies, E-08028 Barcelona - Spain

^[5] Univ Barcelona, Fac Farm & Ciencies Alimentacio, Unitat Farm Tecnol Farmaceut & Fisicoquim, E-08028 Barcelona - Spain

^[6] Univ Barcelona, Inst Nanosci & Nanotechnol IN2UB, E-08028 Barcelona - Spain

^[7] Univ Guadalajara, Ctr Univ Ciencias Biol & Agr, Dept Biol Celular & Mol, Lab Regenerac & Desarrollo Neural, Inst Neurobiol, Zapopan 44600 - Mexico

^[8] Univ Barcelona, Fac Biol, Dept Biol Cellular Fisiol & Immunol, E-08028 Barcelona - Spain

^[9] Fed Univ Sao Carlos UFSCar, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

^[10] Univ Autonoma Chile, Fac Ciencias Salud, Inst Ciencias Biomed, Talca 3460000 - Chile

• Tipo de documento: Artigo de Revisão
• Fonte: PHARMACEUTICALS; v. 11, n. 1 MAR 2018.
• Citações Web of Science: 7

Resumo

Alzheimer's disease (AD) is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid beta peptide (A beta), which form senile plaques, neurofibrillary tangles (NFT) and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM) and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline. Brain insulin resistance, also known as Type 3 diabetes, leads to the increase of A beta production and TAU phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, and cognitive impairment, which are all hallmarks of AD. Moreover, given the complexity of interlocking mechanisms found in late onset AD (LOAD) pathogenesis, more data is being obtained. Recent evidence showed that A beta 42 generated in the brain would impact negatively on the hypothalamus, accelerating the ``peripheral{''} symptomatology of AD. In this situation, A beta 42 production would induce hypothalamic dysfunction that would favour peripheral hyperglycaemia due to down regulation of the liver insulin receptor. The objective of this review is to discuss the existing evidence supporting the concept that brain insulin resistance and altered glucose metabolism play an important role in pathogenesis of LOAD. Furthermore, we discuss AD treatment approaches targeting insulin signalling using anti-diabetic drugs and mTOR inhibitors. (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: 15/26084-1 - Avaliação da ADAM10 plaquetária em demências não-Alzheimer
• Beneficiário: Patricia Regina Manzine Moralles
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado