Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0270736 (Essential tremor)
 404 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Essential tremor (ET) is shown an autosomal dominant mode of inheritance, with no disease-causing gene has been found. Genetic variations in the leucine-rich repeat and lg domain containing nogo receptor-interacting protein genes (LINGO1 and LINGO2) were reported to be associated with an increased risk of developing ET. To explore whether the LINGO4 gene (a homologous gene of the LINGO1 and the LINGO2 genes) plays a role in ET susceptibility, we performed genetic analysis of coding region of the LINGO4 gene in 100 patients with ET from Mainland China. Two nucleotide variants had been identified: (1) T > A transition (rs61746299), predicted to lead to the amino acid change Thr444Ser, and (2) C > T transition (rs1521179), located 12 bp downstream to the end of coding region. To evaluate whether these variants are related to ET susceptibility, we investigated a total of 150 Chinese Han ET patients (77 familial ET and 73 sporadic ET) and 300 sex, age and ethnicity matched normal controls. No significant differences in genotypic and allele distributions between patients and control subjects for rs61746299 and rs1521179 (p = 0.531 and p = 0.867 for genotypic distributions; p = 1.000 and p = 0.844 for allele distributions) were observed, suggesting variants in coding region of the LINGO4 gene may play litter or no role in the risk of ET susceptibility.
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PMID:No evidence of association between the LINGO4 gene and essential tremor in Chinese Han patients. 2210 11

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.
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PMID:LINGO-1 and Neurodegeneration: Pathophysiologic Clues for Essential Tremor. 2343 82

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.
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PMID:Increased LINGO1 in the cerebellum of essential tremor patients. 2453 28