Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic

Autor(es)

Takada, Silvia Honda ^[1] ; Ikebara, Juliane Midori ^[1] ; de Sousa, Erica ^[1] ; Cardoso, Debora Sterzeck ^[1] ; Resende, Rodrigo Ribeiro ^[2] ; Ulrich, Henning ^[3] ; Rueckl, Martin ^[4] ; Ruediger, Sten ^[4] ; Kihara, Alexandre Hiroaki ^{[5, 1]}

Afiliação do(s) autor(es)

^[1] Univ Fed ABC, Lab Neurogenet, Sao Bernardo Do Campo, SP - Brazil

^[2] Univ Fed Minas Gerais, Inst Biol Sci, Cell Signaling & Nanobiotechnol Lab, Dept Biochem & Immunol, Belo Horizonte, MG - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, SP - Brazil

^[4] Humboldt Univ, Inst Phys, Berlin - Germany

^[5] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Neurobiology; v. 54, n. 9, p. 6870-6884, NOV 2017.
• Citações Web of Science: 2

Resumo

It is well known that calcium (Ca2+) is involved in the triggering of neuronal death. Ca2+ cytosolic levels are regulated by Ca2+ release from internal stores located in organelles, such as the endoplasmic reticulum. Indeed, Ca2+ transit from distinct cell compartments follows complex dynamics that are mediated by specific receptors, notably inositol trisphosphate receptors (IP3Rs). Ca2+ release by IP3Rs plays essential roles in several neurological disorders; however, details of these processes are poorly understood. Moreover, recent studies have shown that subcellular location, molecular identity, and density of IP3Rs profoundly affect Ca2+ transit in neurons. Therefore, regulation of IP3R gene products in specific cellular vicinities seems to be crucial in a wide range of cellular processes from neuroprotection to neurodegeneration. In this regard, microRNAs seem to govern not only IP3Rs translation levels but also subcellular accumulation. Combining new data from molecular cell biology with mathematical modelling, we were able to summarize the state of the art on this topic. In addition to presenting how Ca2+ dynamics mediated by IP3R activation follow a stochastic regimen, we integrated a theoretical approach in an easy-to-apply, cell biology-coherent fashion. Following the presented premises and in contrast to previously tested hypotheses, Ca2+ released by IP3Rs may play different roles in specific neurological diseases, including Alzheimer's disease and Parkinson's disease. (AU)

• Processo FAPESP: 11/50151-0 - Fenômenos dinâmicos em redes complexas: fundamentos e aplicações
• Beneficiário: Elbert Einstein Nehrer Macau
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/16711-6 - Relação entre acoplamento celular e microRNAs no desenvolvimento, adaptação e degeneração do sistema nervoso
• Beneficiário: Alexandre Hiroaki Kihara
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/50880-4 - Células-tronco: dos papéis de receptores de cininas e purinas às aplicações terapêuticas
• Beneficiário: Alexander Henning Ulrich
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/50122-0 - Fenômenos dinâmicos em redes complexas: fundamentos e aplicações
• Beneficiário: Elbert Einstein Nehrer Macau
• Linha de fomento: Auxílio à Pesquisa - Temático