Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study is to better define the pathological characteristics of pathologically proven progressive supranuclear palsy (PSP) presenting with the corticobasal syndrome (CBS). PSP is characterized by early falls, vertical supranuclear ophthalmoplegia, and axial rigidity, whereas asymmetric limb features, including rigidity, bradykinesia, apraxia, alien limb phenomena, and cortical sensory loss are characteristic of CBS. We investigated clinicopathological characteristics of 5 cases of PSP that presented with CBS (CBS-PSP). Comprehensive pathological analysis was undertaken to determine the presence of concomitant pathological processes as well as quantitative tau burden in cortical regions of CBS-PSP, compared with 8 typical PSP cases (Typ-PSP). The clinical features in the CBS-PSP cases included asymmetrical features, apraxia, alien limb phenomena, and progressive aphasia. All cases had Parkinsonism, and vertical supranuclear ophthalmoplegia was noted in all but 1 case of CBS-PSP. Secondary neuropathological diagnoses included argyrophilic grain disease (AGD) in 1 of the 8 cases of Typ-PSP, whereas Alzheimer's disease (AD), Lewy body disease, AGD, and vascular disease was found in 3 cases of CBS-PSP. Image analysis of cortical tau burden performed in 8 Typ-PSP and 3 CBS-PSP cases revealed a significant increased tau burden in mid-frontal and inferior-parietal cortices in the CBS-PSP cases. This study demonstrates that when PSP presents as CBS, it is most likely due to either a concurrent cortical pathology from a secondary process such as AD or from the primary pathology of PSP extending into cortical areas that are primarily and commonly affected in CBD.
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PMID:Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome. 1583 57

Hemiparkinsonism-hemiatrophy syndrome (HPHA) is a rare form of parkinsonism, characterized by unilateral parkinsonism, ipsilateral body atrophy and early age of onset. We report a 59-year-old woman with hemiatrophy of her face and upper limb on the left side presenting progressive hemiparkinsonism. Most of the HPHA patients have early age of onset, however, HPHA patients with age of onset over 50 years old have been reported. The clinical features of CBD are partly similar to those of HPHA, therefore it is important to consider HPHA as differential diagnosis of CBD even if the onset is late. In our patient, hemiatrophy was useful to differentiate HPHA from CBD. In previous reports, there was a difference between the dopamine D2 receptor binding capacity of CBD and that of HPHA. While the dopamine D2 receptor binding capacity of CBD was decreased asymmetrically, that of HPHA was not decreased. The PET finding of our patient revealed that asymmetrical reduction of [11C]-CFT uptake, meaning unilateral dopaminergic presynaptic hypofunction. However, [11C]-raclopride uptake, which assesses dopamine D2 receptor binding capacity, was normal. These PET findings are consistent with previous reports on HPHA. In our patient, hemiatrophy and PET findings were useful to diagnose HPHA.
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PMID:[Late onset hemiparkinsonism-hemiatrophy syndrome: a case report]. 1596 Jan 80

Frontotemporal degeneration (FTD), formerly known as Pick's disease has become recognized as a distinct and relatively common entity encompassing behavioural (bvFTD language (PPA) and extrapyramidal (CBD/PSP) presentations. Further clinical subdivisions such as semantic dementia(SD), and pathological subtypes such as mesial temporal sclerosis increase the complexity of diagnosis.The relatively younger age of onset, the typical presentations of syndromes and focal asymmetrical frontotemporal atrophy on imaging allows experienced clinicians to make the diagnosis confidently as long as the overlap between the syndromes is recognized. There is also an overlap with ALS pathologically and clinically. The underlying histology in FTD/Pick complex is ubiquitin positive tau and synuclein negative neuronal inclusions (FTLD-U) in more than half of autopsies and tau positive CBD/PSP/ Pick bodies (FTLD-T) in the rest. The clinical syndromes of bvFTD and SD are likely associated with FTLD-U and PPA/CBDS/PSP with FTLD-T, but there is too much overlap to predict the pathology from the clinical syndromes reliably. The ubiquitin-tau pathological dichotomy is best considered under the Pick complex umbrella to allow for the significant overlap. So far trazodone in behavior and galantamine in aphasia had symptomatic benefit in small trials and SSRI-sand antipsychotics in uncontrolled reports were used as symptomatic therapies. Recent discoveries of tau and progranulin (in the ubiquitin-positive cases) mutations on chromosome 17 and other mutations on chromosome 3 and 9 in the high incidence of autosomal dominant families and a common protein abnormality, the TDP-43 in FTLD-U and ALS are likely to be important in finding therapeutic targets.
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PMID:Clinical features and diagnosis of frontotemporal dementia. 1918 72

Protein kinase A (PKA) is the main receptor for the universal cAMP second messenger. PKA is a tetramer with two catalytic (C) and two regulatory (R) subunits, each including two tandem cAMP binding domains, i.e. CBD-A and -B. Structural investigations of RIalpha have revealed that although CBD-A plays a pivotal role in the cAMP-dependent inhibition of C, the main function of CBD-B is to regulate the access of cAMP to site A. To further understand the mechanism underlying the cross-talk between CBD-A and -B, we report here the NMR investigation of a construct of R, RIalpha-(119-379), which unlike previous fragments characterized by NMR, spans in full both CBDs. Our NMR studies were also extended to two mutants, R209K and the corresponding R333K, which severely reduce the affinity of cAMP for CBD-A and -B, respectively. The comparative NMR analysis of wild-type RIalpha-(119-379) and of the two domain silencing mutations has led to the definition at an unprecedented level of detail of both intra- and interdomain allosteric networks, revealing several striking differences between the two CBDs. First, the two domains, although homologous in sequence and structure, exhibit remarkably different responses to the R/K mutations especially at the beta2-3 allosteric "hot spot." Second, although the two CBDs are reciprocally coupled at the level of local unfolding of the hinge, the A-to-B and B-to-A pathways are dramatically asymmetrical at the level of global unfolding. Such an asymmetric interdomain cross-talk ensures efficiency and robustness in both the activation and de-activation of PKA.
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PMID:Communication between tandem cAMP binding domains in the regulatory subunit of protein kinase A-Ialpha as revealed by domain-silencing mutations. 2020 31

18F-FDOPA PET has been historically used for the evaluation of parkinsonian syndromes in research settings. With the wider availability of PET cameras and 18F-DOPA this method can be used as a clinical diagnostic tool. Current acquisition protocols are simple with a 10 minute static acquisition performed 90 minutes post injection. Criteria for precise visual analysis of the images are defined. The performances of the method are reviewed throughout the literature. The method is very sensitive for detection of IPD versus normal patients. Few studies comparing 18F-FDOPA PET and DAT SPECT did not show any difference in diagnostic accuracy. 18F-FDOPA PET is reliable for evaluation of IPD progression. In general, atypical Parkinson's syndromes cannot be reliably differentiated from IPD since they share a similar nigro-striatal degeneration process. However, some patterns such as the asymmetrical faint homogeneous striatal uptake reduction pattern of CBD can be recognized. The short acquisition protocol, the various indications in oncology of 18F-FDOPA and the high quality of PET images are in favor of this technique in daily clinical practice for the improvement of diagnosis of parkinsonian syndromes.
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PMID:18F-FDOPA PET for the diagnosis of parkinsonian syndromes. 2536 11