Cholinergic system during the progression of Alzheimer's disease: therapeutic implications.
TLDR
Drugs treating the multiple pathologies and clinical symptoms in AD (e.g., M1 cholinoceptor and/or galaninergic drugs) should be considered for a more comprehensive treatment approach for cholinergic dysfunction.Abstract:
Alzheimer's disease (AD) is characterized by a progressive phenotypic downregulation of markers within cholinergic basal forebrain (CBF) neurons, frank CBF cell loss and reduced cortical choline acetyltransferase activity associated with cognitive decline. Delaying CBF neurodegeneration or minimizing its consequences is the mechanism of action for most currently available drug treatments for cognitive dysfunction in AD. Growing evidence suggests that imbalances in the expression of NGF, its precursor proNGF and the high (TrkA) and low (p75(NTR)) affinity NGF receptors are crucial factors underlying CBF dysfunction in AD. Drugs that maintain a homeostatic balance between TrkA and p75(NTR) may slow the onset of AD. A NGF gene therapy trial reduced cognitive decline and stimulated cholinergic fiber growth in humans with mild AD. Drugs treating the multiple pathologies and clinical symptoms in AD (e.g., M1 cholinoceptor and/or galaninergic drugs) should be considered for a more comprehensive treatment approach for cholinergic dysfunction.read more
Citations
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Transient exposure to echinacoside is sufficient to activate Trk signaling and protect neuronal cells from rotenone
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Dual dose-dependent effects of fingolimod in a mouse model of Alzheimer's disease.
Isabel Carreras,Nurgul Aytan,Nurgul Aytan,Ji-Kyung Choi,Christina M. Tognoni,Christina M. Tognoni,Neil W. Kowall,Neil W. Kowall,Bruce G. Jenkins,Alpaslan Dedeoglu,Alpaslan Dedeoglu,Alpaslan Dedeoglu +11 more
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Acteoside and Isoacteoside Protect Amyloid β Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo
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Age-related spatial cognitive impairment is correlated with a decrease in ChAT in the cerebral cortex, hippocampus and forebrain of SAMP8 mice.
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Multi-Target Drug Candidates for Multifactorial Alzheimer’s Disease: AChE and NMDAR as Molecular Targets
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TL;DR: Based on the entwined link of acetylcholinesterase (AChE) and NMDAR, several multifunctional compounds are represented in the rational design of new potential AD medications, investigating the idea and challenges of multi-target drug design.
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