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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Potential role of N-benzylcinnamide in inducing neuronal differentiation from human amniotic fluid mesenchymal stem cells.
Wipawan Thangnipon,Nicha Puangmalai,Nirut Suwanna,Rungtip Soi-ampornkul,Ruchee Phonchai,Naiphinich Kotchabhakdi,Sujira Mukda,Tatsanee Phermthai,Suphakde Julavijitphong,Patoomratana Tuchinda,Saksit Nobsathian +10 more
TL;DR: It is demonstrated that incubation of AF-MSCs, obtained from 16 to 20 week pregnant women, with 10ng/ml bone morphogenetic protein (BMP)-9 for 48h in conditioned medium resulted in transdifferentiation to cholinergic neuronal-like cells, and N-benzylcinnamide may provide a useful adjuvant in BMP-9-induced trans Differentiation of AFMSCs into ultimately cholinergy neurons.
Journal ArticleDOI
The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex
Jayarjun Ethiraj,Thulani H. Palpagama,Clinton Turner,Clinton Turner,Bert van der Werf,Henry J. Waldvogel,Richard Faull,Andrea Kwakowsky +7 more
TL;DR: In this article, the effect of age and sex on the expression of GABAA/BR subunit components in the human brain was examined in the Entorhinal Cortex (ECx) and the dentate gyrus (DG).
Journal ArticleDOI
Conjugation of Aminoadamantane and γ-Carboline Pharmacophores Gives Rise to Unexpected Properties of Multifunctional Ligands.
Sergey O. Bachurin,Galina F. Makhaeva,Elena F. Shevtsova,Alexey Yu. Aksinenko,Vladimir V. Grigoriev,P. N. Shevtsov,Tatiana V. Goreva,Tatiana A. Epishina,Nadezhda V. Kovaleva,Elena A. Pushkareva,N. P. Boltneva,Sofya V. Lushchekina,A. V. Gabrel’yan,V. L. Zamoyski,L. G. Dubova,Elena V. Rudakova,Vladimir P. Fisenko,Elena V. Bovina,Rudy J. Richardson +18 more
TL;DR: In this paper, a series of conjugates of aminoadamantane and γ-carboline, which are basic scaffolds of the known neuroactive agents, memantine and dimebon (Latrepirdine), was synthesized and characterized.
Journal ArticleDOI
Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis on the ascending cholinergic pathways in the rat: a model for Alzheimer's disease.
TL;DR: It is demonstrated that, similarly to the very extensive reduction in the number of ChAT-positive neurons in the nBM, cortical areas Fr1 and HL underwent long-lasting reductions in thenumber of AChE-positive fibers in response to specific cholinergic lesioning of the n BM.
DissertationDOI
Development of High-throughput, Non-invasive Behavioural and Cognitive Tests in Mice to Uncover New Mechanisms of Abnormal Cognition and Behaviour
TL;DR: On further investigation, deletion of Frrs1l was found to cause increased neonatal mortality and abnormalities in activity, co-ordination, muscle strength, cognition and body weight, as well as seizures.
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