title: Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic.
abstract: 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.
authors: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil.
authors: Silvia Honda
authors: SH
authors: Takada
authors: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil.
authors: Juliane Midori
authors: JM
authors: Ikebara
authors: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil.
authors: Erica
authors: E
authors: de Sousa
authors: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil.
authors: Débora Sterzeck
authors: DS
authors: Cardoso
authors: Cell Signaling and Nanobiotechnology Laboratory, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors: Rodrigo Ribeiro
authors: RR
authors: Resende
authors: Departamento de Bioquímíca, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Henning
authors: H
authors: Ulrich
authors: Institute of Physics, Humboldt University at Berlin, Berlin, Germany.
authors: Martin
authors: M
authors: Rückl
authors: Institute of Physics, Humboldt University at Berlin, Berlin, Germany.
authors: Sten
authors: S
authors: Rüdiger
authors: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil. alexandrekihara@gmail.com.|Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil. alexandrekihara@gmail.com.
authors: Alexandre Hiroaki
authors: AH
authors: Kihara
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology; D037181:Lectins, C-Type / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology
chemical_list: C470184:CLECL1 protein, human; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D037181:Lectins, C-Type; D008565:Membrane Proteins
keywords: ALS; Amyotrophic lateral sclerosis; Huntington’s disease; SCA; Spinocerebellar ataxia; miRNA