Quantitative and Functional Analyses of Spastin in the Nervous System: Implications for Hereditary Spastic Paraplegia

Hereditary spastic paraplegia (HSP) refers to a group of neurological disorders involving the degeneration of motor neurons. Due to their clinical and genetic heterogeneity, finding common effective therapeutics is difficult. Therefore, a better understanding of the common pathological mechanisms is necessary. The role of several HSP genes/proteins is linked to the endolysosomal and autophagic pathways, suggesting a functional convergence. Furthermore, impairment of these pathways is particularly interesting since it has been linked to other neurodegenerative diseases, which would suggest that the nervous system is particularly sensitive to the disruption of the endolysosomal and autophagic systems. In this review, we will summarize the involvement of HSP proteins in the endolysosomal and autophagic pathways in order to clarify their functioning and decipher some of the pathological mechanisms leading to HSP.

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Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement

Journal of Child Neurology ◽

10.1177/0883073816639718 ◽

2016 ◽

Vol 31 (9) ◽

pp. 1114-1119 ◽

Cited By ~ 18

Author(s):

Leslie Hotchkiss ◽

Sandra Donkervoort ◽

Meganne E. Leach ◽

Payam Mohassel ◽

Diana X. Bharucha-Goebel ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Hereditary Spastic Paraplegia ◽

De Novo ◽

Central Nervous System Involvement ◽

Spastic Paraplegia ◽

De Novo Mutations ◽

System Involvement

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Hereditary Spastic Paraplegia: Beyond Clinical Phenotypes toward a Unified Pattern of Central Nervous System Damage

Radiology ◽

10.1148/radiol.14141715 ◽

2015 ◽

Vol 276 (1) ◽

pp. 207-218 ◽

Cited By ~ 14

Author(s):

Federica Agosta ◽

Marina Scarlato ◽

Edoardo G. Spinelli ◽

Elisa Canu ◽

Sara Benedetti ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Hereditary Spastic Paraplegia ◽

Spastic Paraplegia ◽

Central Nervous System Damage ◽

Clinical Phenotypes

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Human diseases associated with NTE gene

Ecological genetics ◽

10.17816/ecogen16327 ◽

2020 ◽

Author(s):

Pavel A. Melentev ◽

Olga E Agranovich ◽

Svetlana V Sarantseva

Keyword(s):

Nervous System ◽

Cerebellar Ataxia ◽

Clinical Features ◽

Hereditary Spastic Paraplegia ◽

Gene Mutations ◽

Spastic Paraplegia ◽

Protein Activity ◽

Activity Inhibition ◽

Current Review ◽

Pure Cerebellar Ataxia

Evolutionary conserved NTE gene is important for survival and functioning of nervous system cells, its dysfunction leads to various pathologies. Here we describe characteristics of different disorders induced by NTE protein activity inhibition (OPIDN) or by NTE gene mutations: hereditary spastic paraplegia (SPG39), Boucher-Neuhaser, Gordon Holmes, Laurence-Moon, Oliver-McFarlane syndromes, Leber congenital amaurosis, pure cerebellar ataxia. Current review summarises accumulated data about clinical features of NTE associated diseases, presenting them in a historical way of biomedical studies, and observes molecular and genetic causes of these disorders.

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Fulgence Raymond (1844–1910), regrettably forgotten successor of Jean-Martin Charcot

Clinical and Translational Neuroscience ◽

10.1177/2514183x19880387 ◽

2019 ◽

Vol 3 (2) ◽

pp. 2514183X1988038 ◽

Cited By ~ 2

Author(s):

Olivier Walusinski

Keyword(s):

Nervous System ◽

Hereditary Spastic Paraplegia ◽

Current Knowledge ◽

Nervous System Diseases ◽

Spastic Paraplegia ◽

Relevant Today ◽

Biographical Account ◽

Jean Martin Charcot

Fulgence Raymond (1844–1910) succeeded Jean-Martin Charcot (1825–1893) to the Chair of Nervous System Diseases. As famous as Charcot remains, Raymond has been forgotten. After a brief biographical account, we will present a few examples of his work still relevant today: hemichorea, Raymond-Cestan syndrome, hereditary spastic paraplegia and acute ascendant paralysis. In each case, his accurate clinical and anatomopathological descriptions are accompanied by aetiological hypotheses that are remarkably prescient with regard to current knowledge. Strongly committed to teaching, he published most of his lessons every year. They remain highly relevant historically, and sometimes for other reasons, as we shall see. We hope to show that Raymond does not deserve to be forgotten.

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