Cholinergic treatments for Alzheimer's disease

Roberts, F. F.; Lazareno, Sebastian

doi:10.1042/bst0170076

Cited by 18 publications

(5 citation statements)

References 6 publications

(5 reference statements)

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“…A "rational" approach to cholinergic replacement pharmacotherapy in AD would ideally account for the following: the existence of multiple subtypes of receptors with varied roles in governing neurotransmission; the limitation of addressing one neurotransmitter system when several degenerate; the occurrence of neuropeptides colocalized in cholinergic neurons (for example, galanin, substance P, and vasoactive intestinal polypeptide); the progression of neurodegeneration; and problems with disposition of drugs and regulation of receptors. Although the results with certain cholinomimetic agents have been positive in treatment trials in AD, [193][194][195] neither these drugs nor others have produced consistent or substantial benefit to patients. The low efficacy of the cholinomimetic agents studied thus far may be attributed to oversimplified attempts to normalize a functionally and pathologically complex set of brain systems.…”

Section: Pharmacologic Manipulation Of Muscarinic Receptors For Ad Ormentioning

confidence: 99%

The Potential for Muscarinic Receptor Subtype-Specific Pharmacotherapy for Alzheimer's Disease

McKinney

Coyle

1991

Mayo Clinic Proceedings

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In several neurodegenerative disorders, including Alzheimer's disease, a loss of the cholinergic projections of the basal forebrain to the cerebral cortex and hippocampus occurs. Studies of the anatomic and physiologic characteristics of these ascending cholinergic systems suggest that they are important in processing information and in memory function. Muscarinic receptors are situated at various critical control points in these pathways. Activation of postsynaptic muscarinic receptors often increases the excitability of neurons; thus, the signal-to-noise ratio for sensory processing is enhanced. In addition, muscarinic receptors negatively control cholinergic tone at presynaptic sites. Molecular biologic methods have disclosed the existence of five muscarinic receptors, which are coupled to different second messenger systems. The evidence reviewed suggests that at least four of the five muscarinic receptor genes are expressed as functional receptor proteins in the neocortex and hippocampal formation. On the basis of the current information about their pharmacologic properties and coupling mechanisms in nervous tissue, drugs that selectively affect subtypes of muscarinic receptors could enhance cortical cholinergic function and thereby ameliorate certain cognitive impairments in Alzheimer's disease.

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Section: Pharmacologic Manipulation Of Muscarinic Receptors For Ad Ormentioning

confidence: 99%

The Potential for Muscarinic Receptor Subtype-Specific Pharmacotherapy for Alzheimer's Disease

McKinney

Coyle

1991

Mayo Clinic Proceedings

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“…Pharmacological manipulations also support a critical role for the cholinergic system in memory 2 40 41 . The cholinomimetic strategy driven by the cholinergic hypothesis eventually led to 4 out of 5 FDA-approved drugs for AD 2 42 . However, these cholinesterase inhibitors (ChEIs) eased only some of the symptoms without modifying the disease process 43 , leading to disappointment with and questioning of the cholinergic hypothesis.…”

Section: Discussionmentioning

confidence: 99%

GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability

Singh

Cheng

et al. 2016

Sci Rep

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Why certain diseases primarily affect one specific neuronal subtype rather than another is a puzzle whose solution underlies the development of specific therapies. Selective basal forebrain cholinergic (BFC) neurodegeneration participates in cognitive impairment in Alzheimer’s disease (AD), yet the underlying mechanism remains elusive. Here, we report the first recapitulation of the selective BFC neuronal loss that is typical of human AD in a mouse model termed GAP. We created GAP mice by crossing Tg2576 mice that over-express the Swedish mutant human β-amyloid precursor protein gene with G protein-coupled receptor kinase-5 (GRK5) knockout mice. This doubly defective mouse displayed significant BFC neuronal loss at 18 months of age, which was not observed in either of the singly defective parent strains or in the wild type. Along with other supporting evidence, we propose that GRK5 deficiency selectively renders BFC neurons more vulnerable to degeneration.

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“…The compound crystallizes in the triclinic space group PI (No. 2) with a = 9.070(3) A, b = 10.827(3) A, c = 13.029(4) A; a = 68.07-(2)6,0 = 82.03(3)°, 7 = 77.30(3)0; V = 1155.67 (7) A, Z = 2, = 1.339 cm-3. A total of 2908 independent reflections were collected between 3°< 29 < 110°b y the 9/29 scan method.…”

Section: Procedures For Determination Of Acetylcholinesterasementioning

confidence: 99%

“…Therapeutic applications exist for AChE inhibitors in management of myasthenia gravis (5). More recently, the postulate that a cholinergic deficiency is associated with Alzheimer's disease has led to investigation of AChE inhibitors in this therapeutic context (6)(7)(8)(9).…”

Section: Introduction Chart Imentioning

confidence: 99%

Carbamates of (hydroxyphenoxy)methyl heteroaromatic salts as acetylcholinesterase inhibitors and protective agents against organophosphorus compounds

Sundberg¹,

Dalvie²,

Cordero³

et al. 1993

Chem. Res. Toxicol.

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Cholinergic treatments for Alzheimer's disease

Cited by 18 publications

References 6 publications

The Potential for Muscarinic Receptor Subtype-Specific Pharmacotherapy for Alzheimer's Disease

The Potential for Muscarinic Receptor Subtype-Specific Pharmacotherapy for Alzheimer's Disease

GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability

Carbamates of (hydroxyphenoxy)methyl heteroaromatic salts as acetylcholinesterase inhibitors and protective agents against organophosphorus compounds

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