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
More filters
Journal ArticleDOI
Improvement of cognitive performance by a nutraceutical formulation: Underlying mechanisms revealed by laboratory studies.
TL;DR: In this article, the optimal degree of neuronal protection is derived by combinations of, rather than individual, compounds, which are particularly effective at delaying or improving cognitive performance in the early stages of Mild Cognitive Impairment and Alzheimer's disease.
Journal ArticleDOI
A twenty-year journey exploring coumarin-based derivatives as bioactive molecules
Leonardo Pisani,Marco Catto,Giovanni Muncipinto,Orazio Nicolotti,Antonio Carrieri,Maria Luisa Rullo,Angela Stefanachi,Francesco Leonetti,Cosimo Altomare +8 more
TL;DR: The main scientific results of the 20-years investigation on the coumarin core are reported, exploited by the research group headed by Prof. Angelo Carotti either as a scaffold or a pharmacophore moiety in designing novel biologically active small molecules.
Journal ArticleDOI
TrkA-mediated endocytosis of p75-CTF prevents cholinergic neuron death upon γ-secretase inhibition.
María Luisa Franco,Irmina García-Carpio,Raquel Comaposada-Baró,Juan J Escribano-Saiz,Lucía Chávez-Gutiérrez,Marçal Vilar +5 more
TL;DR: In this article, the authors showed that GSI treatment induces the oligomerization of p75CTF leading to the cell death of BFCNs, and that this event is dependent on TrkA activity.
Journal ArticleDOI
Effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on MK-801-induced schizophrenia models.
Oguz Mutlu,Tomáš Páleníček,Nikola Pinterova,Klára Šíchová,Jiří Horáček,Kristina Holubova,Cyril Höschl,Ales Stuchlik,Faruk Erden,Karel Vales +9 more
TL;DR: AKH had no effect in sensorimotor gating deficits in the PPI test in schizophrenia model while AKH improved memory in the schizophrenia model of MK‐801.
Book ChapterDOI
Alzheimer's Disease: From Animal Models to the Human Syndrome
Erika Orta-Salazar,Isaac Vargas‐Rodríguez,Susana A. Castro-Chavira,Alfredo I. Feria‐Velasco,Sofía Díaz-Cintra +4 more
TL;DR: This review compares and evaluates the phenotypes of different AD animal models, on the basis of the specific objectives of each study, with the purpose of encompassing their contributions to the comprehension of the AD signs and symptoms in humans.
References
More filters
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.
Related Papers (5)
Selective loss of central cholinergic neurons in alzheimer's disease
Peter Davies,A.J.F. Maloney +1 more
A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease
Mark H. Tuszynski,Mark H. Tuszynski,Leon J. Thal,Leon J. Thal,Mary Pay,David P. Salmon,Hoi Sang U,Roy A.E. Bakay,Piyush M. Patel,Armin Blesch,H. Lee Vahlsing,H. Lee Vahlsing,Gilbert Ho,Gang Tong,Steven G. Potkin,James H. Fallon,Lawrence A. Hansen,Elliott J. Mufson,Jeffrey H. Kordower,Christine M. Gall,James M. Conner +20 more