Calpains are intracellular calcium-dependent cysteine proteases ubiquitously expressed
in mammals. CAPN1 encodes calpain-1, one of the major calpain isoforms expressed in the Central Nervous
System (CNS) [
1
,
2
]. Growing evidence suggests that calpain-1 is involved in several molecular processes
and pathways in the CNS such as synaptic plasticity, neuronal migration, neuronal
necrosis and maintenance [
3
,
4
,
5
]. Recently, rare homozygous or compound-heterozygous pathogenic variants in the CAPN1 gene (MIM: 114220) have been reported in eight individuals from three families with an adult-onset
(mean age 28.5 years; range 19–39), complicated form of Hereditary Spastic Paraplegia (HSP). In addition
to mild-to-moderate spastic paraplegia with slowly progressive course, patients variably
presented upper limb hyperreflexia, dysarthria, gait ataxia and sensory axonal neuropathy
[
[6]
]. Later, Wang and colleagues identified CAPN1 biallelic pathogenic variants in six patients from four families who presented with
progressive ataxia and spasticity, with onset at about 20 years [
[7]
]; mild-to-moderate cerebellar atrophy was evident on brain MRI in three cases [
[7]
].Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A comparative study of soluble calcium-dependent proteolytic activity in brain.J. Neurobiol. 1986; 17: 15-28
- Distribution of calpains I and II in rat brain.J. Neurosci. 1986; 6: 3103-3111
- Calpain in the CNS: from synaptic function to neurotoxicity.Sci. Signal. 2008; 1: re1
- Distinct roles for mu-calpain and m-calpain in synaptic NMDAR-mediated neuroprotection and extrasynaptic NMDAR-mediated neurodegeneration.J. Neurosci. 2013; 33: 18880-18892
- A molecular brake controls the magnitude of long-term potentiation.Nat. Commun. 2014; 5: 3051
- Mutations in CAPN1 cause autosomal-recessive hereditary spastic paraplegia.Am. J. Hum. Genet. 2016; 98: 1038-1046
- Defects in the CAPN1 Gene result in alterations in cerebellar development and cerebellar ataxia in mice and humans.Cell Rep. 2016; 16: 79-91
Article info
Publication history
Published online: May 10, 2017
Accepted:
May 9,
2017
Received in revised form:
April 7,
2017
Received:
January 30,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
