Hereditary Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery

Loading...
Thumbnail Image
File version

Version of Record (VoR)

Author(s)
Mackay-Sim, Alan
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
2021
Size
File type(s)
Location
Abstract

Hereditary spastic paraplegia (HSP) is a diverse group of Mendelian genetic disorders affecting the upper motor neurons, specifically degeneration of their distal axons in the corticospinal tract. Currently, there are 80 genes or genomic loci (genomic regions for which the causative gene has not been identified) associated with HSP diagnosis. HSP is therefore genetically very heterogeneous. Finding treatments for the HSPs is a daunting task: a rare disease made rarer by so many causative genes and many potential mutations in those genes in individual patients. Personalized medicine through genetic correction may be possible, but impractical as a generalized treatment strategy. The ideal treatments would be small molecules that are effective for people with different causative mutations. This requires identification of disease-associated cell dysfunctions shared across genotypes despite the large number of HSP genes that suggest a wide diversity of molecular and cellular mechanisms. This review highlights the shared dysfunctional phenotypes in patient-derived cells from patients with different causative mutations and uses bioinformatic analyses of the HSP genes to identify novel cell functions as potential targets for future drug treatments for multiple genotypes.

Journal Title

Brain Sciences

Conference Title
Book Title
Edition
Volume

11

Issue

3

Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Item Access Status
Note
Access the data
Related item(s)
Subject

Neurosciences

Psychiatry (incl. psychotherapy)

Cognitive and computational psychology

Persistent link to this record
Citation

Mackay-Sim, A, Hereditary Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery, Brain Sciences, 11 (3), pp. 403

Collections