Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Grb10-Interacting GYF Protein 2 (GIGYF2) was initially identified through its interaction with Grb10, an adapter protein that binds activated IGF-I and insulin receptors. The GIGYF2 gene maps to human chromosome 2q37 within a region linked to familial Parkinson's disease (PARK11 locus), and association of GIGYF2 mutations with Parkinson's disease has been described in some but not other recent publications. This study investigated the consequences of Gigyf2 gene disruption in mice. Gigyf2 null mice undergo apparently normal embryonic development, but fail to feed and die within the first 2 post-natal days. Heterozygous Gigyf2(+/-) mice survive to adulthood with no evident metabolic or growth defects. At 12-15 months of age, the Gigyf2(+/-) mice begin to exhibit motor dysfunction manifested as decreased balance time on a rotating horizontal rod. This is associated with histopathological evidence of neurodegeneration and rare intracytoplasmic Lewy body-like inclusions in spinal anterior horn motor neurons. There are alpha-synuclein positive neuritic plaques in the brainstem and cerebellum, but no abnormalities in the substantia nigra. Primary cultured embryo fibroblasts from Gigyf2 null mice exhibit decreased IGF-I-stimulated IGF-I receptor tyrosine phosphorylation and augmented ERK1/2 phosphorylation. These data provide further evidence for an important role of GIGYF2 in age-related neurodegeneration and IGF pathway signaling.
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PMID:GIGYF2 gene disruption in mice results in neurodegeneration and altered insulin-like growth factor signaling. 1974 60

Meeus et al. (2009) reported no pathogenic mutations in a comprehensive genetic analysis of the entire GRB10-interacting GYF protein-2 gene (GIGYF2) in a Belgian series of both familial and sporadic patients with Parkinson's disease (PD). Although we initially proposed that GIGYF2 corresponds to the PARK11 locus, in familial PD, we found no causative variations in a follow-up study in which GIGYF2 was screened in an independent series of 185 patients with autosomal dominant PD, mostly of French origin. Together, these results do not support a major role of GIGYF2 in PD.
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PMID:Follow-up study of the GIGYF2 gene in French families with Parkinson's disease. 2000 41

The Grb10-Interacting GYF Protein-2 gene (GIGYF2), located in the chromosomal region 2q36-q37, has been reported as a PARK11 gene with a causal role in familial Parkinson's disease (PD) in Italian and French populations. However, there is no comprehensive study of GIGYF2 gene conducted in Chinese patients with PD from mainland China. The 27 coding exons and intron/exon boundaries of the GIGYF2 gene were sequenced in 300 sporadic patients with Parkinson's disease. Eight heterozygous and one homozygous novel missense variants were identified in nine patients with PD, and not in 300 controls. p.Leu580Phe locates in the GYF domain and might interrupt the potentially function of GIGYF2 protein. Another variant Gln979stop encodes a truncated protein. In conclusion, we identified nine novel variants in GIGYF2 gene, which might be associated with PD in the Chinese population.
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PMID:Novel GIGYF2 gene variants in patients with Parkinson's disease in Chinese population. 2017 31

Grb10-Interacting GYF Protein-2 (GIGYF2) is a candidate gene for PARK11 locus. To date, seven different GIGYF2 missense mutations have been identified in patients with familial Parkinson disease (PD) of European descent. To clarify the pathogenic role of GIGYF2 in PD, we analyzed the frequency of GIGYF2 mutations in 389 Japanese patients with PD (including 93 patients with late-onset familial PD, 276 with sporadic PD, and 20 with a single heterozygous mutation in the PD-associated genes), and 336 Japanese normal controls, by direct sequencing and/or high-resolution melting analysis. None of the reported GIGYF2 mutations or digenic mutations were detected. Two novel non-synonymous variants were identified (p.Q1211delQ and p.H1023Q), however, we could not determine their roles in PD. In summary, we found no evidence for PD-associated roles of GIGYF2 mutations. Our data suggest that GIGYF2 is unlikely to play a major role in PD in Japanese patients, similar to other populations.
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PMID:No evidence for pathogenic role of GIGYF2 mutation in Parkinson disease in Japanese patients. 2064 Nov 65

GIGYF2 has been reported as a candidate gene for PARK11-linked Parkinson's disease (PD). Heterozygous knockout of GIGYF2 results in neurodegeneration, suggesting important roles for GIGYF2 (Grb10 interacting GYF protein 2) in the CNS. In this study, we used novel GIGYF2 antibodies to clarify the distribution and function of GIGYF2. GIGYF2 was widely expressed, most highly in the pancreas and testis, and moderately in brain, lung, liver, kidney and spleen. In the brain, GIGYF2 was tightly associated with membrane in the S3 fraction, and localised in neuronal perikarya and proximal dendrites. Immunohistochemical analysis indicated sites of GIGYF2 localisation throughout the mouse brain, with high levels in the cerebral cortex, hippocampus, cerebellum, olfactory bulb and brainstem nuclei, but low levels in the substantia nigra and striatum. GIGYF2 was present in endosomes immunopositive for Rab4 and Grb10. Expression of GIGYF2 altered insulin-like growth factor-1 (IGF-1) receptor trafficking and enhanced IGF-1-induced extracellular signal-regulated kinase 1/2 phosphorylation, but not IGF-1 receptor or serine/threonine protein kinase Akt phosphorylation. There were no significant differences in signalling activation between cells expressing wild-type and putative PD-associated mutant GIGYF2. In PD brains, GIGYF2 did not localise to Lewy bodies. Our findings indicate a role for GIGYF2 in the regulation of signalling at endosomes, but no contribution of GIGYF2 to the pathogenesis of PD.
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PMID:GIGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF-1-induced ERK1/2 activation. 2067 Mar 74


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