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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Nerve growth factor: basic studies and possible therapeutic applications
Luigi Manni,Maria Luisa Rocco,Patrizia Bianchi,Marzia Soligo,Morena Guaragna,Samuele Paparo Barbaro,Luigi Aloe +6 more
TL;DR: These studies published from the laboratory have shown that topical application of NGF possesses a protective action on human pressure ulcer, corneal ulcer and glaucoma, supporting the therapeutic potential of N GF.
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Brain Changes in Alzheimer's Disease Patients with Implanted Encapsulated Cells Releasing Nerve Growth Factor
Daniel Ferreira,Eric Westman,Helga Eyjolfsdottir,Per Almqvist,Göran Lind,Bengt Linderoth,Åke Seiger,Kaj Blennow,Azadeh Karami,Taher Darreh-Shori,Maria Kristoffersen Wiberg,Andrew Simmons,Lars-Olof Wahlund,Lars Wahlberg,Maria Eriksdotter +14 more
TL;DR: MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain support the idea that encapsulated biodELivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.
Journal ArticleDOI
Gene expression levels assessed by CA1 pyramidal neuron and regional hippocampal dissections in Alzheimer's disease.
TL;DR: Single population studies of specific neurons and intrinsic circuits will likely yield informative gene expression profile data that may be subthreshold and/or underrepresented in regional studies with an admixture of cell types.
Journal ArticleDOI
Cotinine reduces amyloid-β aggregation and improves memory in Alzheimer's disease mice.
Valentina Echeverria,Ross Zeitlin,Sarah Burgess,Sagar Patel,Arghya Barman,Garima Thakur,Magorzota Mamcarz,Magorzota Mamcarz,Li Wang,David B. Sattelle,Daniel A. Kirschner,Takashi Mori,Roger M. Leblanc,Rajeev Prabhakar,Gary W. Arendash +14 more
TL;DR: Cotinine reduced Aβ deposition, improved working and reference memories, and inhibited Aβ oligomerization in the brains of transgenic (Tg) 6799 AD mice, suggesting that cotinine may be an excellent therapeutic candidate for the treatment of AD.
Journal ArticleDOI
Dissecting the involvement of tropomyosin-related kinase A and p75 neurotrophin receptor signaling in NGF deficit-induced neurodegeneration
TL;DR: It is demonstrated that inhibiting TrkA signaling activates Aβ accumulation and that different streams of AD neurodegeneration are related in complex ways to Trk a versus p75NTR signaling.
References
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Journal ArticleDOI
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