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
REST/NRSF-induced changes of ChAT protein expression in the neocortex and hippocampus of the 3xTg-AD mouse model for Alzheimer's disease.
E. Orta-Salazar,E. Orta-Salazar,Azucena Aguilar-Vázquez,H. Martínez-Coria,S. Luquín-De Anda,Martha C. Rivera-Cervantes,Carlos Beas-Zarate,Alfredo Feria-Velasco,Sofía Díaz-Cintra +8 more
TL;DR: The increased REST/NRSF expression reported here and its effect on the regulatory region for ChAT transcription could explain the decreased expression of ChAT in the 3xTg-AD mouse; these findings may be associated with the degeneration observed in AD.
Journal ArticleDOI
Anti-Alzheimer’s Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential
Md. Tanvir Kabir,Md. Sahab Uddin,Philippe Jeandet,Talha Bin Emran,Saikat Mitra,Ghadeer M. Albadrani,Amany A. Sayed,Mohamed M. Abdel-Daim,Jesus Simal-Gandara +8 more
TL;DR: In this paper, a review of drugs derived from marine life that can be useful in AD treatment and also summarize the therapeutic agents that are currently used to treat Alzheimer's disease. But, there is no available therapy that can cure AD.
Book ChapterDOI
Memory deficits in aging and neurological diseases.
TL;DR: Current understanding of the impact of normal aging on memory and what is known about its mechanisms are focused on, and pathological mechanisms behind the cause of dementia in Alzheimer's disease are reviewed.
Journal ArticleDOI
Nerve growth factor (NGF) and pro-NGF increase low-density lipoprotein (LDL) receptors in neuronal cells partly by different mechanisms: role of LDL in neurite outgrowth
Hai Thi Do,Hai Thi Do,Céline Bruelle,Céline Bruelle,Dan Duc Pham,Dan Duc Pham,Matti Jauhiainen,Ove Eriksson,Laura Korhonen,Laura Korhonen,Laura Korhonen,Dan Lindholm,Dan Lindholm +12 more
TL;DR: It is shown that NGF and simvastatin are able to stimulate lipoprotein uptake by neurons with a positive effect on neurite outgrowth and increases in LDLRs and lipop protein particles in neurons could play a functional role during brain development, in neuroregeneration and after brain injuries.
Journal ArticleDOI
Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta.
Michalina Hebda,Marek Bajda,Anna Więckowska,Natalia Szałaj,Anna Pasieka,Dawid Panek,Justyna Godyń,Tomasz Wichur,Damijan Knez,Stanislav Gobec,Barbara Malawska +10 more
TL;DR: Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors and their ability to cross the blood-brain barrier (BBB) was confirmed in vitro in the parallel artificial membrane permeability BBB assay.
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