Molecular Investigations of Protein Aggregation in the Pathogenesis of Amyotrophic Lateral Sclerosis

被引:26
作者
Duranti, Elisa [1 ]
Villa, Chiara [1 ]
机构
[1] Univ Milano Bicocca, Sch Med & Surg, I-20900 Monza, Italy
关键词
amyotrophic lateral sclerosis; aggregation; neurodegenerative diseases; FRONTOTEMPORAL LOBAR DEGENERATION; NUCLEAR IMPORT RECEPTOR; RNA-BINDING PROTEINS; NEURON DISEASES ALS; SUPEROXIDE-DISMUTASE; ALPHA-SYNUCLEIN; PHASE-SEPARATION; MISFOLDED PROTEINS; ALZHEIMERS-DISEASE; DROSOPHILA MODEL;
D O I
10.3390/ijms24010704
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disorder characterized by selective loss of lower and upper motor neurons (MNs) in the brain and spinal cord, resulting in paralysis and eventually death due to respiratory insufficiency. Although the fundamental physiological mechanisms underlying ALS are not completely understood, the key neuropathological hallmarks of ALS pathology are the aggregation and accumulation of ubiquitinated protein inclusions within the cytoplasm of degenerating MNs. Herein, we discuss recent insights into the molecular mechanisms that lead to the accumulation of protein aggregates in ALS. This will contribute to a better understanding of the pathophysiology of the disease and may open novel avenues for the development of therapeutic strategies.
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页数:18
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共 155 条
[41]   The chaperone HSPB8 reduces the accumulation of truncated TDP-43 species in cells and protects against TDP-43-mediated toxicity [J].
Crippa, Valeria ;
Cicardi, Maria Elena ;
Ramesh, Nandini ;
Seguin, Samuel J. ;
Ganassi, Massimo ;
Bigi, Ilaria ;
Diacci, Chiara ;
Zelotti, Elena ;
Baratashvili, Madina ;
Gregory, Jenna M. ;
Dobson, Christopher M. ;
Cereda, Cristina ;
Pandey, Udai Bhan ;
Poletti, Angelo ;
Carra, Serena .
HUMAN MOLECULAR GENETICS, 2016, 25 (18) :3908-3924
[42]   Motoneuronal and muscle-selective removal of ALS-related misfolded proteins [J].
Crippa, Valeria ;
Galbiati, Mariarita ;
Boncoraglio, Alessandra ;
Rusmini, Paola ;
Onesto, Elisa ;
Giorgetti, Elisa ;
Cristofani, Riccardo ;
Zito, Arianna ;
Poletti, Angela .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2013, 41 :1598-1604
[43]   Understanding the role of TDP-43 and FUS/TLS in ALS and beyond [J].
Da Cruz, Sandrine ;
Cleveland, Don W. .
CURRENT OPINION IN NEUROBIOLOGY, 2011, 21 (06) :904-919
[44]   Disease-linked TDP-43 hyperphosphorylation suppresses TDP-43 condensation and aggregation [J].
da Silva, Lara A. Gruijs ;
Simonetti, Francesca ;
Hutten, Saskia ;
Riemenschneider, Henrick ;
Sternburg, Erin L. ;
Pietrek, Lisa M. ;
Gebel, Jakob ;
Doetsch, Volker ;
Edbauer, Dieter ;
Hummer, Gerhard ;
Stelzl, Lukas S. ;
Dormann, Dorothee .
EMBO JOURNAL, 2022, 41 (08)
[45]   The role of FUS gene variants in neurodegenerative diseases [J].
Deng, Hao ;
Gao, Kai ;
Jankovic, Joseph .
NATURE REVIEWS NEUROLOGY, 2014, 10 (06) :337-348
[46]   α-Synuclein in motor neuron disease:: an immunohistologic study [J].
Doherty, MJ ;
Bird, TD ;
Leverenz, JB .
ACTA NEUROPATHOLOGICA, 2004, 107 (02) :169-175
[47]   ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import [J].
Dormann, Dorothee ;
Rodde, Ramona ;
Edbauer, Dieter ;
Bentmann, Eva ;
Fischer, Ingeborg ;
Hruscha, Alexander ;
Than, Manuel E. ;
Mackenzie, Ian R. A. ;
Capell, Anja ;
Schmid, Bettina ;
Neumann, Manuela ;
Haass, Christian .
EMBO JOURNAL, 2010, 29 (16) :2841-2857
[48]   Classification and basic pathology of Alzheimer disease [J].
Duyckaerts, Charles ;
Delatour, Benoit ;
Potier, Marie-Claude .
ACTA NEUROPATHOLOGICA, 2009, 118 (01) :5-36
[49]   TDP-43 and FUS en route from the nucleus to the cytoplasm [J].
Ederle, Helena ;
Dormann, Dorothee .
FEBS LETTERS, 2017, 591 (11) :1489-1507
[50]   SOD1A4V aggregation alters ubiquitin homeostasis in a cell model of ALS [J].
Farrawell, Natalie E. ;
Lambert-Smith, Isabella ;
Mitchell, Kristen ;
McKenna, Jessie ;
McAlary, Luke ;
Ciryam, Prajwal ;
Vine, Kara L. ;
Saunders, Darren N. ;
Yerbury, Justin J. .
JOURNAL OF CELL SCIENCE, 2018, 131 (11)