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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Journal ArticleDOI
The cholinergic system in aging and neuronal degeneration.
Reinhard Schliebs,Thomas Arendt +1 more
TL;DR: Observed changes in the expression of NGF, its precursor proNGF, the high and low NGF receptors, trkA and p75NTR, respectively, changes in acetylcholine release, high-affinity choline uptake, as well as alterations in muscarinic and nicotinic acetyl choline receptor expression may contribute to the cholinergic dysfunction.
Journal ArticleDOI
The cholinergic system in the pathophysiology and treatment of Alzheimer's disease.
Harald Hampel,M.-Marsel Mesulam,A. Claudio Cuello,Martin R. Farlow,Ezio Giacobini,George T. Grossberg,Ara S. Khachaturian,Andrea Vergallo,Enrica Cavedo,Peter J. Snyder,Peter J. Snyder,Zaven S. Khachaturian +11 more
TL;DR: The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as the authors look ahead to future combination therapies that address symptoms as well as disease progression.
Journal ArticleDOI
The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in Human and Rodent Studies: A Review
TL;DR: This review will focus on the current epidemiological evidence of arsenic neurotoxicity in children and adults, with emphasis on cognitive dysfunction, including learning and memory deficits and mood disorders, and new studies focusing on therapeutic strategies to combat arsenic toxicity including the use of selenium and zinc.
Journal ArticleDOI
Nicotinic ACh receptors as therapeutic targets in CNS disorders
TL;DR: The functional makeup and expression of the nAChRs in mammalian brain, and their role as targets in neurodegenerative diseases, neurodevelopmental disorders, and neuropathic pain are discussed.
Journal ArticleDOI
Drug treatments in Alzheimer's disease.
TL;DR: Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials and results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution.
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