Role of non-neuronal cells in neurorepair: a focus on proteinopathy and neurodegeneration

Rodríguez-Carreiro, Santiago1,2,3,4; Nogales, Maria del Carmen1; Jiménez-Galán, David1; Carmona-Lorenzo, Sara1; Caro-Martín, Alicia1; Navarro, Elisa1,2,3,4; Esteras, Noemí1,2,3,5,6

1Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Madrid, Spain

2Neurochemistry Research Institute, Complutense University of Madrid, Madrid, Spain

3CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, Madrid, Spain

4Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain

5Group of Neurodegenerative Diseases, Hospital Universitario 12 de Octubre Research Institute (imas12), Madrid, Spain

6Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK

*Correspondence to: Elisa Navarro, PhD, elisnava@ucm.es; Noemí Esteras, PhD, nesteras@ucm.es.

#Both authors contributed equally to this work.Funding: This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities to EN (PID2022-139936OA-I00) and NE (PID2022-137011OA-I00/AEI/10.13039/501100011033/FEDER, EU) and a Ramon y Cajal Fellowship to NE (RYC2021-034267-I) funded by the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU”/PRTR. SRC is a predoctoral fellow supported by the FPU Program (Ministry of Education and Universities).

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Regenerative Medicine Reports 1(1):p 31-51, September 2024. | DOI: 10.4103/REGENMED.REGENMED-D-24-00005

Abstract

Despite advances in biomedicine, therapies that prevent neuronal loss have not been effective. Several strategies targeting the defining markers of the main neurodegenerative diseases, such as amyloid beta or tau, which are pivotal in Alzheimer’s disease or frontotemporal dementia, or α-synuclein, the leading actor in Parkinson’s disease, have shown limited success. Nevertheless, these proteins do not act only in neurons but also are part of a network involving non-neuronal brain cells, such as astrocytes, microglia and oligodendrocytes, as well as the peripheral immune system. In this review, we aim to cover the role of non-neuronal central and peripheral cells in proteinopathies associated with α-synuclein, amyloid-β and tau, with the objective of identifying new options for regenerative medicine aimed at neuroprotection and neurorepair.

非神经细胞在蛋白病、神经变性和再生医学中的作用：叙述性综述

摘要

尽管生物医学在不断进步，但防止神经元丧失的疗法仍不奏效。针对主要神经退行性疾病的决定性标志物，如阿尔茨海默病或额颞叶痴呆的关键标志物淀粉样β蛋白或 tau，或帕金森病的罪魁祸首α-突触核蛋白的几种干预策略成效有限。然而，这些蛋白质并不仅仅作用于神经元，它们还涉及非神经元脑细胞，如星形胶质细胞、小胶质细胞和少突胶质细胞，以及外周免疫系统。文章介绍了非神经元中枢和外周细胞在α-突触核蛋白、淀粉样蛋白β和tau相关蛋白病中的作用，目的是为该类疾病的神经保护和修复相关寻找新的再生医学干预途径。