Abstract
Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurological disorders characterized by pathophysiologic hallmark of length-dependent distal axonal degeneration of the corticospinal tracts. The prominent features of this pathological condition are progressive spasticity and weakness of the lower limbs. To date, 72 spastic gait disease-loci and 55 spastic paraplegia genes (SPGs) have been identified. All modes of inheritance (autosomal dominant, autosomal recessive, and X-linked) have been described. Recently, a late onset spastic gait disorder with maternal trait of inheritance has been reported, as well as mutations in genes not yet classified as spastic gait disease. Several cellular processes are involved in its pathogenesis, such as membrane and axonal transport, endoplasmic reticulum membrane modeling and shaping, mitochondrial function, DNA repair, autophagy, and abnormalities in lipid metabolism and myelination processes. Moreover, recent evidences have been found about the impairment of endosome membrane trafficking in vesicle formation and about the involvement of oxidative stress and mtDNA polymorphisms in the onset of the disease. Interactome networks have been postulated by bioinformatics and biological analyses of spastic paraplegia genes, which would contribute to the development of new therapeutic approaches.
| Original language | English |
|---|---|
| Pages (from-to) | 518-539 |
| Number of pages | 22 |
| Journal | Experimental Neurology |
| Volume | 261 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Hereditary spastic paraplegia
- Molecular genetics
- Neurodegenerative mechanisms
- Neurology
- Phenotype
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience
- Medicine(all)
Cite this
Hereditary spastic paraplegia : Clinical-genetic characteristics and evolving molecular mechanisms. / Lo Giudice, Temistocle; Lombardi, Federica; Santorelli, Filippo Maria; Kawarai, Toshitaka; Orlacchio, Antonio.
In: Experimental Neurology, Vol. 261, 2014, p. 518-539.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hereditary spastic paraplegia
T2 - Clinical-genetic characteristics and evolving molecular mechanisms
AU - Lo Giudice, Temistocle
AU - Lombardi, Federica
AU - Santorelli, Filippo Maria
AU - Kawarai, Toshitaka
AU - Orlacchio, Antonio
PY - 2014
Y1 - 2014
N2 - Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurological disorders characterized by pathophysiologic hallmark of length-dependent distal axonal degeneration of the corticospinal tracts. The prominent features of this pathological condition are progressive spasticity and weakness of the lower limbs. To date, 72 spastic gait disease-loci and 55 spastic paraplegia genes (SPGs) have been identified. All modes of inheritance (autosomal dominant, autosomal recessive, and X-linked) have been described. Recently, a late onset spastic gait disorder with maternal trait of inheritance has been reported, as well as mutations in genes not yet classified as spastic gait disease. Several cellular processes are involved in its pathogenesis, such as membrane and axonal transport, endoplasmic reticulum membrane modeling and shaping, mitochondrial function, DNA repair, autophagy, and abnormalities in lipid metabolism and myelination processes. Moreover, recent evidences have been found about the impairment of endosome membrane trafficking in vesicle formation and about the involvement of oxidative stress and mtDNA polymorphisms in the onset of the disease. Interactome networks have been postulated by bioinformatics and biological analyses of spastic paraplegia genes, which would contribute to the development of new therapeutic approaches.
AB - Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurological disorders characterized by pathophysiologic hallmark of length-dependent distal axonal degeneration of the corticospinal tracts. The prominent features of this pathological condition are progressive spasticity and weakness of the lower limbs. To date, 72 spastic gait disease-loci and 55 spastic paraplegia genes (SPGs) have been identified. All modes of inheritance (autosomal dominant, autosomal recessive, and X-linked) have been described. Recently, a late onset spastic gait disorder with maternal trait of inheritance has been reported, as well as mutations in genes not yet classified as spastic gait disease. Several cellular processes are involved in its pathogenesis, such as membrane and axonal transport, endoplasmic reticulum membrane modeling and shaping, mitochondrial function, DNA repair, autophagy, and abnormalities in lipid metabolism and myelination processes. Moreover, recent evidences have been found about the impairment of endosome membrane trafficking in vesicle formation and about the involvement of oxidative stress and mtDNA polymorphisms in the onset of the disease. Interactome networks have been postulated by bioinformatics and biological analyses of spastic paraplegia genes, which would contribute to the development of new therapeutic approaches.
KW - Hereditary spastic paraplegia
KW - Molecular genetics
KW - Neurodegenerative mechanisms
KW - Neurology
KW - Phenotype
UR - http://www.scopus.com/inward/record.url?scp=84906495186&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906495186&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2014.06.011
DO - 10.1016/j.expneurol.2014.06.011
M3 - Article
C2 - 24954637
AN - SCOPUS:84906495186
VL - 261
SP - 518
EP - 539
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
ER -