Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0752347 (Dementia with Lewy bodies)
 1,653 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-Parkinsonian, irreversible, selective monoamine oxidase (MAO)-B inhibitors, selegiline (deprenyl, (R)-N-methyl-N-(1-phenylpropan-2-yl) prop-2-yn-1-amine) and rasagiline (Azilect, N-propargyl-1(R)-aminoindan), have been proven to possess neuroprotective/neurorestorative activities in cell cultures and animal models of neurodegenerative diseases. Structure-activity studies provide evidence that neuroprotection is associated with some intrinsic pharmacological action of the propargylamine moiety in these drugs. This indication and recent therapeutic approaches, entailing new drug candidates possessing diverse pharmacological properties and acting on multiple targets, have stimulated the development of two multifunctional chimeric propargylamine-derivatives: 1) ladostigil (TV3326, [(N-propargyl-(3R) 1-(R)-aminoindan-5yl)-ethyl methyl carbamate)], which combines the pharmacophore of rasagiline, with the carbamate moiety of the cholinesterase inhibitor rivastigmine, as a potential treatment for Alzheimer's disease and Lewy body disease; and 2) M30 5-[(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline], where the propargylamine moiety of rasagiline was embedded onto the backbone of the neuroprotective and brain permeable iron chelator 8-hydroxyquinoline-derivative, VK28 as a potential treatment for various neurodegenerative disorders. Both multifunctional propargylamine-derivatives were found to possess neuroprotective and anti-apoptotic properties. An additional and new neuroprotective effect, shared by the propargylamine-derivative compounds, is related to their ability to regulate the processing of amyloid-beta protein precursor (AbetaPP) by the non-amyloidogenic alpha-secretase pathway. This effect was shown to involve activation of p42/44 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signaling pathway. This review will summarize and discuss current research, focused on the effect of propargylamine-related derivatives on the proteolytic processing of AbetaPP and signal transduction mechanisms.
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PMID:Propargylamine containing compounds as modulators of proteolytic cleavage of amyloid-beta protein precursor: involvement of MAPK and PKC activation. 2055 37

Alzheimer's disease and dementia with Lewy bodies are the most common neurodegenerative dementias in old age. Accurate diagnosis of these conditions has important clinical implications because they tend to be confounded. In the brain of Alzheimer's disease patients amyloid-beta is produced in excess and deposited as plaques, forming the hallmark of this condition. Lymphocytes have been implicated in the process of amyloid-beta removal and inflammation occurrence. Here we investigated peripheral amyloid-beta1-42-specific T-cells by multicolor flow cytometry to simultaneously detect and characterize activation markers and cell signaling proteins (phospho-protein kinase C) in patients with Alzheimer's disease or Lewy body dementia and in healthy controls. Results indicate that only Alzheimer's disease patients display small subsets of peripheral amyloid-beta1-42-specific T-cells, characterized by bright expression of phosphorylated-protein kinase C-delta or -zeta whose significance although discussed, is far from being understood. The identification of such subsets, anyhow, may strongly contribute to distinguish Alzheimer's disease from dementia with Lewy bodies, opening possible new routes to early therapeutic strategies.
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PMID:Amyloid-specific T-cells differentiate Alzheimer's disease from Lewy body dementia. 2233 Jan 73