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.
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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.
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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.
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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.
References
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Journal ArticleDOI
Neurotrophin signaling through the p75 neurotrophin receptor.
TL;DR: It remains a major challenge to link the various p75NTR binding proteins to specific p75nTR-dependent functions, but the identification of p 75NTR interactors and signaling pathways has sparked new directions in p75 NTR research, and will provide a better understanding of this enigmatic receptor.
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Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment.
Steven T. DeKosky,Milos D. Ikonomovic,Scot D. Styren,Laurel A. Beckett,Stephen R. Wisniewski,David A. Bennett,Elizabeth J. Cochran,Jeffrey H. Kordower,Elliott J. Mufson +8 more
TL;DR: Cognitive deficits in MCI and early AD are not associated with the loss of ChAT and occur despite regionally specific upregulation, suggesting that the earliest cognitive deficits in AD involve brain changes other than simply cholinergic system loss.
Journal ArticleDOI
Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies
TL;DR: This review will initially discuss recent results indicating a link between cholinergic mechanisms and the pathogenic events that characterize AD, notably amyloid-β peptides, and animal models of dementia will be discussed in light of the relationship between basal forebrain cholinerg hypofunction and cognitive impairments in AD.
Journal ArticleDOI
Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor.
TL;DR: It is demonstrated that p75NTR is capable of signaling independently of the trk neurotrophin receptor (p140trk) and that ceramide may be a mediator in neurotroph in biology.
Journal ArticleDOI
Extracellular-signal-regulated kinase signalling in neurons.
TL;DR: This work has shown that multiple second messengers, such as cyclic adenosine monophosphate, protein kinase A, calcium, and diacylglycerol, can control ERK signalling via the small G proteins Ras and Rap1, and allows us to begin to develop a model to understand both the control of ERKs at the subcellular level and the generation ofERK signal specificity.
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