Increased LINGO1 in the cerebellum of essential tremor patients.
Identifieur interne : 000546 ( Main/Exploration ); précédent : 000545; suivant : 000547Increased LINGO1 in the cerebellum of essential tremor patients.
Auteurs : Charlotte Delay [Canada] ; Cyntia Tremblay ; Elodie Brochu ; Sarah Paris-Robidas ; Vincent Emond ; Ali H. Rajput ; Alex Rajput ; Frédéric CalonSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Cerebellum (metabolism), Cerebellum (pathology), Essential Tremor (pathology), Female, Gene Expression Regulation (physiology), Humans, Male, Membrane Proteins (genetics), Membrane Proteins (metabolism), Middle Aged, Nerve Tissue Proteins (genetics), Nerve Tissue Proteins (metabolism), RNA, Messenger (metabolism), White Matter (metabolism), White Matter (pathology).
- MESH :
- chemical , genetics : Membrane Proteins, Nerve Tissue Proteins.
- metabolism : Cerebellum, Membrane Proteins, Nerve Tissue Proteins, RNA, Messenger, White Matter.
- pathology : Cerebellum, Essential Tremor, White Matter.
- physiology : Gene Expression Regulation.
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged.
Abstract
Essential tremor (ET) is the most prevalent adult-onset movement disorder. Despite its health burden, no clear pathognomonic sign has been identified to date because of the rarity of clinicopathological studies. Moreover, treatment options are still scarce and have not significantly changed in the last 30 years, underscoring the urgent need to develop new treatment avenues. In the recent years, leucine-rich repeat (LRR) and immunoglobulin (Ig) domain-containing Nogo receptor-interacting proteins 1 and 2 (LINGO1 and LINGO2, respectively) have been increasingly regarded as possible ET modulators due to emerging genetic association studies linking LINGO with ET. We have investigated LINGO protein and messenger RNA (mRNA) expression in the cerebellum of patients with ET, patients with Parkinson's disease (PD), and a control group using Western immunoblotting and in situ hybridization. Protein levels of LINGO1, but not LINGO2, were significantly increased in the cerebellar cortex of ET patients compared with controls, particularly in individuals with longer disease duration. Compared with controls, LINGO1 protein levels were increased in the cerebellar white matter of PD and ET patients but, for the latter, only when disease duration exceeded 20 years. However, no alteration in LINGO1 mRNA was observed between groups in either the cerebellar cortex or the white matter. We observed alterations in LINGO expression in diseased brain that seemed to progress along with the disease, being initiated in the cerebellar cortex before reaching the white matter. Because LINGO up-regulation has been identified as a potential pathological response to ongoing neurodegenerative processes, the present data suggest that LINGO1 is a potential drug target for ET.
DOI: 10.1002/mds.25819
PubMed: 24531928
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">Essential tremor (ET) is the most prevalent adult-onset movement disorder. Despite its health burden, no clear pathognomonic sign has been identified to date because of the rarity of clinicopathological studies. Moreover, treatment options are still scarce and have not significantly changed in the last 30 years, underscoring the urgent need to develop new treatment avenues. In the recent years, leucine-rich repeat (LRR) and immunoglobulin (Ig) domain-containing Nogo receptor-interacting proteins 1 and 2 (LINGO1 and LINGO2, respectively) have been increasingly regarded as possible ET modulators due to emerging genetic association studies linking LINGO with ET. We have investigated LINGO protein and messenger RNA (mRNA) expression in the cerebellum of patients with ET, patients with Parkinson's disease (PD), and a control group using Western immunoblotting and in situ hybridization. Protein levels of LINGO1, but not LINGO2, were significantly increased in the cerebellar cortex of ET patients compared with controls, particularly in individuals with longer disease duration. Compared with controls, LINGO1 protein levels were increased in the cerebellar white matter of PD and ET patients but, for the latter, only when disease duration exceeded 20 years. However, no alteration in LINGO1 mRNA was observed between groups in either the cerebellar cortex or the white matter. We observed alterations in LINGO expression in diseased brain that seemed to progress along with the disease, being initiated in the cerebellar cortex before reaching the white matter. Because LINGO up-regulation has been identified as a potential pathological response to ongoing neurodegenerative processes, the present data suggest that LINGO1 is a potential drug target for ET.</div>
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<name sortKey="Emond, Vincent" sort="Emond, Vincent" uniqKey="Emond V" first="Vincent" last="Emond">Vincent Emond</name>
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<name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name>
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