Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochemical markers for the major neurotransmitter systems were measured in the brains of 5 patients who had died with neuropathologically confirmed progressive supranuclear palsy. A marked nigrostriatal dopamine deficiency, observed in 4 of the 5 patients, was sufficient to explain the parkinsonian features (especially bradykinesia) observed in patients with progressive supranuclear palsy. Dopamine concentrations, however, were normal in the nucleus accumbens, hypothalamus, and temporal cortex. Brain noradrenalin, serotonin, gamma-aminobutyric acid, and aspartic acid levels were generally normal. Normal brain choline acetyltransferase activity (the marker enzyme for cholinergic neurons) in the 2 patients with severe dementia suggests that, at least in some patients, the cognitive impairment in this disorder is likely to be related to noncholinergic neurotransmitter system changes. The glutamic acid concentration was elevated in many brain areas in 3 of the 5 patients studied.
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PMID:Progressive supranuclear palsy: relationship between extrapyramidal disturbances, dementia, and brain neurotransmitter markers. 241 69

Parkinson's disease (PD) is a chronic neurodegenerative disease, and there is no cure for it at present. Recent research has indicated a link between type 2 diabetes mellitus (T2DM) and PD, which suggested that a treatment to improve insulin resistance for T2DM may be useful for PD patients. Glucose-dependent insulinotropic polypeptide (GIP) belongs to the incretin hormone family, which can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. In the present study, a novel long-lasting GIP analogue, D-Ala2-GIP-glu-PAL, has been tested in an acute PD mouse model induced by four 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal injections. D-Ala2-GIP-glu-PAL treatment (25 nmol/kg ip.) for 7 days after MPTP treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement balance of mice. D-Ala2-GIP-glu-PAL treatment also restored tyrosine hydroxylase (TH) positive dopaminergic neuron numbers in the substantia nigra and TH levels in the striatum. D-Ala2-GIP-glu-PAL also reduced the chronic inflammation response as seen in astrocyte and microglia activation in the substantia nigra pars compacta (SNpc). D-Ala2-GIP-glu-PAL reversed the reduction of synapse numbers (synaptophysin levels), decreased the ratio of growth factor and apoptosis signaling molecules Bax/Bcl-2, and improved the decrease of p-CREB(S133) growth factor signaling in the substantia nigra. Therefore, D-Ala2-GIP-glu-PAL promotes cell survival of dopaminergic neuron in the SNpc by activating the cAMP/PKA/CREB growth factor second messenger pathway that also inhibits apoptosis. The present results demonstrate that D-Ala2-GIP-glu-PAL shows promise as a novel treatment of PD.
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PMID:Neuroprotective effects of a GIP analogue in the MPTP Parkinson's disease mouse model. 2645 62