Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives

Author:

Olivero Pablo12ORCID,Lozano Carlo123,Sotomayor-Zárate Ramón4,Meza-Concha Nicolás1,Arancibia Marcelo1,Córdova Claudio1,González-Arriagada Wilfredo25,Ramírez-Barrantes Ricardo6ORCID,Marchant Ivanny12ORCID

Affiliation:

1. Laboratorio de Estructura y Función Celular, Escuela de Medicina, Facultad de Medicina, Universidad de Valparaíso, Hontaneda 2664, 2341386 Valparaíso, Chile

2. Centro Interoperativo en Ciencias Odontológicas y Médicas, Universidad de Valparaíso, Valparaíso, Chile

3. Servicio de Anatomía Patológica, Hospital Carlos van Buren, San Ignacio 725, Valparaíso, Chile

4. Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile

5. Patología y Diagnóstico Oral, Facultad de Odontología, Universidad de Valparaíso, Valparaíso, Chile

6. Escuela de Tecnologia Medica, Universidad Andres Bello, Quillota 980, 2531015 Viña del Mar, Chile

Abstract

Proteostasis involves processes that are fundamental for neural viability. Thus, protein misfolding and the formation of toxic aggregates at neural level, secondary to dysregulation of the conservative mechanisms of proteostasis, are associated with several neuropsychiatric conditions. It has been observed that impaired mitochondrial function due to a dysregulated proteostasis control system, that is, ubiquitin-proteasome system and chaperones, could also have effects on neurodegenerative disorders. We aimed to critically analyze the available findings regarding the neurobiological implications of proteostasis on the development of neurodegenerative and psychiatric diseases, considering the mitochondrial role. Proteostasis alterations in the prefrontal cortex implicate proteome instability and accumulation of misfolded proteins. Altered mitochondrial dynamics, especially in proteostasis processes, could impede the normal compensatory mechanisms against cell damage. Thereby, altered mitochondrial functions on regulatory modulation of dendritic development, neuroinflammation, and respiratory function may underlie the development of some psychiatric conditions, such as schizophrenia, being influenced by a genetic background. It is expected that with the increasing evidence about proteostasis in neuropsychiatric disorders, new therapeutic alternatives will emerge.

Funder

Fondo Nacional de Desarrollo Científico y Tecnológico

Publisher

Hindawi Limited

Subject

Clinical Neurology,Neurology

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