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

The precursor of the non-Abeta-component of Alzheimer's disease (AD) amyloid (NACP, alpha-synuclein) aggregates into insoluble filaments of Lewy bodies (LBs) in Parkinson's disease (PD) and dementia with LBs (DLB). The microtubule-associated protein tau is an integral component of filaments of neurofibrillary tangles (NFTs). NFTs are occasionally found in brains of PD and DLB; however, the presence of NFTs or tau-epitopes within LB-containing neurons is rare. Double-immunofluorescence study and peroxidase-immunohistochemical study in serial sections, performed to examine the co-localization of tau- and NACP-epitopes in the brainstem of PD and DLB, demonstrated that four different epitopes of tau including phosphorylation-dependent and independent ones were present in a minority of LBs, but more often than previously considered. A tau (tau2)-epitope was localized to filaments in the outer layers of brainstem-type LBs by immunoelectron microscopy. Therefore, we conclude that tau is incorporated into filaments in certain LBs. Extensive investigation has enabled us to classify this co-localization into four types: type 1, LBs with ring-shaped tau-immunoreactivity; type 2, LBs surrounded by NFTs; type 3, NACP- and tau-immunoreactive filamentous and granular masses; and type 4, NACP- and tau-immunoreactive dystrophic neurites. This study raises a new question whether aggregation and hyperphosphorylation of tau in PD and DLB are triggered by the collapse of intraneuronal organization of microtubules due to NACP-filament aggregation in neuronal perikarya and axons.
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PMID:Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. 1052 10

Whole-genome epistasis analysis may add a new layer of knowledge to whole-genome association studies, permitting the identification of new candidate genes which are completely transparent during conventional single-locus analysis. We present the first whole-genome conditional two-locus analysis in Parkinson's disease (PD). We scanned the entire genome and selected markers that interacted with a set of well-known loci previously associated to PD (SNCA, Parkin, LRRK2, UCHL1, DJ-1, PINK and MAPT). Our work describes several loci potentially related to PD risk which interact with SNCA, PARK1 and LRRK2 markers. We propose conditional whole-genome two-locus association analysis as a valuable method that might be helpful in re-analysing and re-interpreting data from whole-genome association studies.
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PMID:Whole-genome conditional two-locus analysis identifies novel candidate genes for late-onset Parkinson's disease. 1915 51

In the past decade, a number of genetic causes of parkinsonism have been identified. As a consequence, clinicians have to consider an increasing range of differential diagnoses when confronted with a patient with parkinsonism with a positive family history. While well-established monogenic forms with PARK acronyms have been reviewed extensively, less emphasis has been placed on other inherited conditions that may also present with signs of parkinsonism or even mimic idiopathic Parkinson's disease clinically. In this review, we focus on three different scenarios in patients with an overall early age of onset of parkinsonism: (i) atypical features in patients with mutations in one of the "PARK" genes; (ii) classical parkinsonism due to mutations in "other than-PARK" genes or yet other genes where parkinsonism may be a well-recognized, concomitant, or even an isolated feature; (iii) atypical parkinsonism in other genetic disorders which are, however, typically characterized by features other than parkinsonism. Atypical features in patients from Group I include, for example, a slower disease course (PARK2, PARK6, PARK7) or dementia (PARK1/4, PARK14). Conditions in Group II have been designated by a DYT or SCA acronym (for example, DYT5 or SCA3) and also include patients with heterozygous GBA mutations, mitochondrial gene mutations. Group III comprises mutations in the FMR1, MAPT, GRN, ATP7B, PANK2, FBXO7, CHAC, FTL1, Huntingtin, JPH3 genes, and a number of even rarer, miscellaneous conditions.
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PMID:Hereditary parkinsonism: Parkinson disease look-alikes--an algorithm for clinicians to "PARK" genes and beyond. 1973 92

In 1997 a mutation in the a-synuclein (SNCA) gene was associated with familial autosomal dominant Parkinson's disease (PD). Since then, several loci (PARK1-15) and genes have been linked to familial forms of the disease. There is now sufficient evidence that six of the so far identified genes at PARK loci (a-synuclein, leucine-rich repeat kinase 2, parkin, PTEN-induced putative kinase 1, DJ-1, and ATP13A2) cause inherited forms of typical PD or parkinsonian syndromes. Other genes at non-PARK loci (MAPT, SCA1, SCA2, spatacsin, POLG1) cause syndromes with parkinsonism as one of the symptoms. The majority of PD cases are however sporadic "idiopathic" forms, and the recent application of genome-wide screening revealed almost 20 genes that might contribute to disease risk. In addition, increasing evidence suggests that epigenetic mechanisms, such as DNA methylation, histone modifications, and small RNA-mediated mechanisms, could regulate the expression of PD-related genes.
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PMID:Genetics and epigenetics of Parkinson's disease. 2262

In the molecular era, the study of neurogenetic disorders in relict populations provides an opportunity to discover new genes by linkage studies and to establish clearer genotype-phenotype correlations in large cohorts of individuals carrying the same mutation. The Basque people are one of the most ancient populations living in Europe and represent an excellent resource for this type of analysis in certain genetic conditions. Our objective was to describe neurogenetic disorders reported in the Basque population due to the presence of ancestral mutations or an accumulation of cases or both. We conducted a search in PubMed with the terms: Basque, neurogenetic disorders, genetic risk, and neurological disorders. We identified nine autosomal and two recessive disorders in the Basque population attributable to ancestral mutations (such as in PNRP, PARK8, FTDP-TDP43, LGMD2A, VCP, c9ORF72, and CMT4A), highly prevalent (DM1) or involving unique mutations (PARK1 or MAPT). Other genes were reported for their role as protective/risk factors in complex diseases such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease. At the present time, when powerful sequencing techniques are identifying large numbers of genetic variants associated with unique phenotypes, the scrutiny of these findings in genetically homogeneous populations can help analyze genotype-phenotype correlations.
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PMID:Neurogenetic disorders in the Basque population. 2544 Sep 84