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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Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior.
Joseph M. Hall,Lisa M. Savage +1 more
TL;DR: A novel mechanism by which exercise can modulate the mature cholinergic/nestin neuronal phenotype leading to improved neurotransmitter function as well as enhanced learning and memory is demonstrated.
Journal ArticleDOI
Swedish Nerve Growth Factor Mutation (NGFR100W) Defines a Role for TrkA and p75NTR in Nociception
Kijung Sung,Luiz F. Ferrari,Wanlin Yang,ChiHye Chung,Xiaobei Zhao,Yingli Gu,Suzhen Lin,Kai Zhang,Bianxiao Cui,Matthew L. Pearn,Michael T. Maloney,William C. Mobley,Jon D. Levine,Chengbiao Wu +13 more
TL;DR: These studies provide evidence that NGFR100W retains trophic support capability through TrkA and one aspect of its nociceptive signaling, but fails to engage p75NTR signaling pathways, and suggest that wtNGF acts via TrKA to regulate the delayed priming of nOCiceptive responses.
Journal ArticleDOI
Impaired NGF/TrkA Signaling Causes Early AD-Linked Presynaptic Dysfunction in Cholinergic Primary Neurons.
Valentina Latina,Silvia Caioli,Cristina Zona,Maria Teresa Ciotti,G. Amadoro,Pietro Calissano +5 more
TL;DR: This study provides new insights on the earliest molecular mechanisms underlying the loss of synaptic/trafficking proteins and, then, of synapes integrity which occurs in vulnerable basal forebrain population at preclinical stages of neuropathology and offers prime presynaptic-based molecular target to extend the therapeutic time-window of NGF action in the strategy of improving its neuroprotective in vivo intervention in affected patients.
Journal ArticleDOI
Early endosomal abnormalities and cholinergic neuron degeneration in amyloid-β protein precursor transgenic mice
Jennifer H.K. Choi,Gurjinder Kaur,Matthew J. Mazzella,Jose Morales-Corraliza,Efrat Levy,Paul M. Mathews +5 more
TL;DR: The idea that increased expression of A βPP and AβPP metabolites in neurons is sufficient to drive early endosomal abnormalities in vivo is supported, and that disruption of the endocytic system is likely to contribute to basal forebrain cholinergic vulnerability.
Journal ArticleDOI
Protective Effects of Wogonin against Alzheimer's Disease by Inhibition of Amyloidogenic Pathway
TL;DR: Wogonin, one of the major active constituting components in Scutellaria baicalensis, has the neuroprotective effects on amyloid-β peptides- (Aβ-) induced toxicity and may be a promising multifunctional drug candidate for AD.
References
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Journal ArticleDOI
Mild cognitive impairment as a diagnostic entity
TL;DR: It is suggested that the diagnosis of mild cognitive impairment can be made in a fashion similar to the clinical diagnoses of dementia and AD, and an algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI.
Journal ArticleDOI
Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.
Bengt Winblad,Katie Palmer,Miia Kivipelto,Vesna Jelic,Laura Fratiglioni,Lars-Olof Wahlund,Agneta Nordberg,Lars Bäckman,Marilyn S. Albert,Ove Almkvist,Hiroyuki Arai,Hans Basun,Kaj Blennow,M. J. de Leon,Charles DeCarli,Timo Erkinjuntti,Ezio Giacobini,Caroline Graff,John Hardy,Clifford R. Jack,Anthony F. Jorm,Karen Ritchie,C M van Duijn,Pieter Jelle Visser,Ronald C. Petersen +24 more
TL;DR: A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics.
Journal ArticleDOI
Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.
Robert D. Terry,Eliezer Masliah,David P. Salmon,Nelson Butters,Richard DeTeresa,Robert Hill,Lawrence A. Hansen,Robert Katzman +7 more
TL;DR: Both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of patients with Alzheimer's disease and 9 neuropathologically normal subjects reveal very powerful correlations with all three psychological assays.
Journal ArticleDOI
Selective loss of central cholinergic neurons in alzheimer's disease
Peter Davies,A.J.F. Maloney +1 more
Journal ArticleDOI
Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
TL;DR: Antisera raised against synthetic peptides corresponding to these different human tau isoforms demonstrate that multiple tau protein isoforms are incorporated into the neurofibrillary tangles of Alzheimer's disease.
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