Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently several responsible genes for hereditary neurodegenerative disorders were identified. In some of them the gene products were found to be aggregated. In the case of Alzheimer disease beta protein and apolipoprotein E accumulated in senile plaques. In CAG repeat diseases the polyglutamine aggregates in neuronal nuclei. More recently alpha synuclein accumulates in Lewy bodies in Parkinson disease and tau protein accumulates in NFT of hereditary frontotemporal dementia with tau mutation. Those results suggested that the responsible gene products accumulates in the lesion which the products involve in. However, presenilin which is one of the genes for familial Alzheimer disease accumulates in NFT and on the other hand its mutation changes the production ratio of beta 1-42/40, suggesting that the abnormal gene products not simply accumulate the lesion that it involved. The gene products accumulate in different lesions such as in nuclei of polyglutamine diseases, extracellular plaque and cytoplasm of prion disease and extracellular plaques in Alzheimer disease. Some of them are ubiquitinated and some of them are not. Thus the accumulating process in these disorders seems apparently same but is essentially different. We should study more precisely each pathological process of those disorders.
 ...
PMID:[Neuronal cell death--what we can see and what we cannot]. 1037 83

C57BL/6J mice develop genetically determined age-related hippocampal granular deposits that have some similarities to lesions seen in the brains of human patients with tau protein related neurodegenerative disorders ("tauopathies"). We sought to identify the genetic loci responsible for these in an F2 intercross of inbred mouse strains C57BL/6J and DBA/2J, using quantitative trait locus (QTL) analysis. Hippocampal lesions were shown to be PAS positive, H and E negative, and immunoreactive for tau protein and alpha synuclein, but not to Abeta 1-40 or Abeta 1-42, or for ubiquitin. These were quantitated by histomorphometry, and QTL analysis revealed a locus on chromosome 7 with a lod score of 6.5 as well as two suggestive loci on chromosome 10. The genomic data indicate that the genetic basis is complex, but with one locus playing a major role in lesion formation. These lesions may represent a useful model for investigating dysregulation of tau protein in the hippocampus.
 ...
PMID:Genetic loci contributing to age-related hippocampal lesions in mice. 1282 34

In the investigation of disease aetiology, the genome-wide association study (GWAS) provides a hypothesis-free investigation of the broader human genome and, as with all scientific investigations, replication is essential to validate any findings. To date, six GWAS have been performed to investigate the influence of common genetic variation in Parkinson's disease (PD) and only two associations have been replicated: alpha synuclein (SNCA) and microtubule-associated protein tau (MAPT), both PD candidate genes before GWAS. In our population-based study, we genotyped four of the top single-nucleotide polymorphisms (SNPs) from a previous study. By using the identical analytic method and genetic model in our independent sample, we provide evidence for replication of rs1724425 near MAPT (OR = 0.74, P= 0.0163) and rs1564282 in cyclin G-associated kinase (GAK; OR = 1.61, P= 0.0151); rs3775478 of multimerin 1 (MMRN1) (P= 0.30) and rs356229 of SNCA (P= 0.14) did not replicate in our study population. While MAPT has been considered a PD candidate gene and has been observed in association with PD in other GWAS, GAK is a new candidate for investigation in future studies.
 ...
PMID:Replication of GWAS associations for GAK and MAPT in Parkinson's disease. 2105 43

Mild traumatic brain injury (mTBI) is one of the leading predisposing factors in the development of Parkinson's disease (PD). Mild or moderate TBI induces rapid production of tau protein and alpha synuclein (ASNC) in the cerebrospinal fluid (CSF) and in several brain areas. Enhanced tau-phosphorylation and ASNC alters the molecular machinery of the brain leading to PD pathology. Recent evidences show upregulation of constitutive isoform of hemeoxygenase (HO-2) in PD patients that correlates well with the brain pathology. mTBI alone induces profound upregulation of HO-2 immunoreactivity. Thus, it would be interesting to explore whether mTBI exacerbates PD pathology in relation to tau, ASNC and HO-2 expression. In addition, whether neurotrophic factors and stem cells known to reduce brain pathology in TBI could induce neuroprotection in PD following mTBI. In this review role of mesenchymal stem cells (MSCs) and cerebrolysin (CBL), a well-balanced composition of several neurotrophic factors and active peptide fragments using nanowired delivery in PD following mTBI is discussed based on our own investigation. Our results show that mTBI induces concussion exacerbates PD pathology and nanowired delivery of MSCs and CBL induces superior neuroprotection. This could be due to reduction in tau, ASNC and HO-2 expression in PD following mTBI, not reported earlier. The functional significance of our findings in relation to clinical strategies is discussed.
 ...
PMID:Mild traumatic brain injury exacerbates Parkinson's disease induced hemeoxygenase-2 expression and brain pathology: Neuroprotective effects of co-administration of TiO2 nanowired mesenchymal stem cells and cerebrolysin. 3322 35