Dataset Information

LINGO-1 and Neurodegeneration: Pathophysiologic Clues for Essential Tremor.

ABSTRACT: Essential tremor (ET), one of the most common adult-onset movement disorders, has been associated with cerebellar Purkinje cell degeneration and formation of brainstem Lewy bodies. Recent findings suggest that genetic variants of the leucine-rich repeat and Ig domain containing 1 (LINGO-1) gene could be risk factors for ET. The LINGO-1 protein contains both leucine-rich repeat (LRR) and immunoglobulin (Ig)-like domains in its extracellular region, as well as a transmembrane domain and a short cytoplasmic tail. LINGO-1 can form a ternary complex with Nogo-66 receptor (NgR1) and p75. Binding of LINGO-1 with NgR1 can activate the NgR1 signaling pathway, leading to inhibition of oligodendrocyte differentiation and myelination in the central nervous system. LINGO-1 has also been found to bind with epidermal growth factor receptor (EGFR) and induce downregulation of the activity of EGFR-PI3K-Akt signaling, which might decrease Purkinje cell survival. Therefore, it is possible that genetic variants of LINGO-1, either alone or in combination with other genetic or environmental factors, act to increase LINGO-1 expression levels in Purkinje cells and confer a risk to Purkinje cell survival in the cerebellum.Here, we provide a concise summary of the link between LINGO-1 and neurodegeneration and discuss various hypotheses as to how this could be potentially relevant to ET pathogenesis.

SUBMITTER: Zhou ZD

PROVIDER: S-EPMC3569903 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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LINGO-1 and Neurodegeneration: Pathophysiologic Clues for Essential Tremor.

Zhou Zhi-Dong ZD Sathiyamoorthy Sushmitha S Tan Eng-King EK

Tremor and other hyperkinetic movements (New York, N.Y.) 20120220

Essential tremor (ET), one of the most common adult-onset movement disorders, has been associated with cerebellar Purkinje cell degeneration and formation of brainstem Lewy bodies. Recent findings suggest that genetic variants of the leucine-rich repeat and Ig domain containing 1 (LINGO-1) gene could be risk factors for ET. The LINGO-1 protein contains both leucine-rich repeat (LRR) and immunoglobulin (Ig)-like domains in its extracellular region, as well as a transmembrane domain and a short cy ...[more]

PMID: 23439882

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Project description:Essential tremor (ET) is among the most common neurological diseases and it often runs in families. How knowledgeable ET patients and their families are about their disease has been the subject of surprisingly little scholarship.To fill this gap in knowledge, we administered a comprehensive 32-item survey (i.e., questions about etiology, pathophysiology, symptoms and signs, natural history, and treatments) to 427 participants, including 76 ET probands, 74 affected relatives (AFRs), 238 unaffected relatives, and 39 spouses of unaffected relatives, all of whom were participating in two ET family studies. We hypothesized that there would be gaps in knowledge about ET and furthermore, that probands and AFRs would be the most knowledgeable, followed by unaffected relatives and then spouses of unaffected relatives, who would be the least knowledgeable.Overall, ET patients lacked knowledge about their disease. Nearly one-third of probands answered "yes" or "do not know" to the question, "is ET the same or different from the type of tremor that many normal people can get when they become old and frail?" A similar proportion did not know whether children could get ET or they responded "no." Nearly one-fourth of affecteds (i.e., probands and AFRs) did not know whether or to what degree (e.g., very well, moderately well, not well) the symptoms of ET could be medically controlled, and 38.0% either reported that there was no brain surgery for ET or reported that they did not know. Nearly 17% of affecteds did not endorse genes as a cause for ET, which was surprising given the fact that this was a family study of ET. Probands and AFRs were the most knowledgeable, followed by unaffected relatives. Spouses of unaffected relatives were the least knowledgeable.We targeted a large group of ET patients and their families, as this group is perhaps most likely to be informed about the disease. ET patients and their AFRs were more knowledgeable about the features of ET than their family members without ET. Overall, however, knowledge of ET was very limited and this lack of knowledge encompassed all aspects of the disease including its underlying causes, the nature of the symptoms and signs, its natural history and its treatment. Further ET awareness education and programs targeting both families of ET patients and the public would help alleviate this gap in knowledge.

Dataset Information

LINGO-1 and Neurodegeneration: Pathophysiologic Clues for Essential Tremor.

Publications

LINGO-1 and Neurodegeneration: Pathophysiologic Clues for Essential Tremor.

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