Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel

Al-kuraishy, Hayder M.; Jabir, Majid S.; Al-Gareeb, Ali I.; Albuhadily, Ali K.; Albukhaty, Salim; Sulaiman, Ghassan M.; Batiha, Gaber El-Saber

doi:10.1016/j.arr.2023.102119

Cited by 16 publications

(11 citation statements)

References 125 publications

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“… 46 , 47 , 48 AD neuropathology is characterized by extracellular accumulation of mutant amyloid beta (Aβ) peptide and intracellular accumulation of hyper‐phosphorylated tau protein which form neurofibrillary tangles (NFTs). 22 , 49 , 50 , 51 Of note, synaptic abnormalities are involved in AD neuropathology and linked with disease severity and progression of Aβ and NFTs. Both Aβ and NFTs alter the synapses and neuronal circuit resulting in cognitive dysfunction and impairment of the synthesis and the release of BDNF from brain neurons.…”

Section: Bdnf and Neurodegenerative Diseasesmentioning

confidence: 99%

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2024

J Cellular Molecular Medi

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Parkinson's disease (PD) is a neurodegenerative disorder of the brain and is manifested by motor and non‐motor symptoms because of degenerative changes in dopaminergic neurons of the substantia nigra. PD neuropathology is associated with mitochondrial dysfunction, oxidative damage and apoptosis. Thus, the modulation of mitochondrial dysfunction, oxidative damage and apoptosis by growth factors could be a novel boulevard in the management of PD. Brain‐derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase type B (TrkB) are chiefly involved in PD neuropathology. BDNF promotes the survival of dopaminergic neurons in the substantia nigra and enhances the functional activity of striatal neurons. Deficiency of the TrkB receptor triggers degeneration of dopaminergic neurons and accumulation of α‐Syn in the substantia nigra. As well, BDNF/TrkB signalling is reduced in the early phase of PD neuropathology. Targeting of BDNF/TrkB signalling by specific activators may attenuate PD neuropathology. Thus, this review aimed to discuss the potential role of BDNF/TrkB activators against PD. In conclusion, BDNF/TrkB signalling is decreased in PD and linked with disease severity and long‐term complications. Activation of BDNF/TrkB by specific activators may attenuate PD neuropathology.

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Section: Bdnf and Neurodegenerative Diseasesmentioning

confidence: 99%

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2024

J Cellular Molecular Medi

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“…Amyloid-beta protein (A

) is a peptide fragment derived from the hydrolytic cleavage of amyloid precursor protein (APP), a product of the amyloidogenic pathway of APP processing [ 29 , 30 ]. Under normal physiological conditions, A

produced in the body can be degraded by insulin-degrading enzymes and neprilysin and is thereby expelled from the body through physiological activities [ 31 ].…”

Section: Pathophysiology Of Admentioning

confidence: 99%

An Epigenetic Manifestation of Alzheimer's Disease: DNA Methylation

Feng,

Zheng,

Cai

et al. 2024

Actas Esp Psiquiatr

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Alzheimer's disease (AD), the most common form of dementia, has a complex pathogenesis. The number of AD patients has increased in recent years due to population aging, while a trend toward a younger age of onset has arisen, imposing a substantial burden on society and families, and garnering extensive attention. DNA methylation has recently been revealed to play an important role in AD onset and progression. DNA methylation is a critical mechanism regulating gene expression, and alterations in this mechanism dysregulate gene expression and disrupt important pathways, including oxidative stress responses, inflammatory reactions, and protein degradation processes, eventually resulting in disease. Studies have revealed widespread changes in AD patients' DNA methylation in the peripheral blood and brain tissues, affecting multiple signaling pathways and severely impacting neuronal cell and synaptic functions. This review summarizes the role of DNA methylation in the pathogenesis of AD, aiming to provide a theoretical basis for its early prevention and treatment.

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“…APP was first described as a cell-surface receptor and was highlighted as a cell adhesion molecule [75]. APP is a type I transmembrane glycoprotein notorious for its involvement in the pathogenesis of AD through A40 and A42 peptides generated from APP in an amyloidogenic protease pathway in the brain involving β-secretase (BACE-1, -site APP cleaving enzyme, mepapsin 2) and γ-secretase [76]. These amyloid peptides self-assemble to form insoluble plaques and neurofibrillary tangles which detrimentally impact on synaptic function, neuron viability and cognitive processes in the brain, leading to dementia [77][78][79].…”

Section: The Enigmatic and Perplexing Story Of App Processing In Brai...mentioning

confidence: 99%

“…These amyloid peptides self-assemble to form insoluble plaques and neurofibrillary tangles which detrimentally impact on synaptic function, neuron viability and cognitive processes in the brain, leading to dementia [77][78][79]. APP, however, is also processed bysecretase via a non-amyloidogenic pathway; this generates the soluble amyloid precursor sAPPα peptide [76]. sAPPα promotes neuroprotection, synaptic plasticity, memory formation, neurogenesis, neuritogenesis, and reduces amyloid and tau pathology [80][81][82].…”

Section: The Enigmatic and Perplexing Story Of App Processing In Brai...mentioning

confidence: 99%

Amyloid, a Jekyll and Hyde Molecule Inducing Neuronal Decline and Cognitive Dysfunction is Also a Unique Molecular Template used in Nano-electronics, Light Capture Photovoltaics, and Biosensors in Neuromorphic Computing.

Melrose,

Smith

2024

Preprint

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Amyloid self-assembled from amyloid peptides βΑ40 or βΑ42 is notorious for its neurotoxic effects in plaque and neurofibrillary tangle formations leading to neuron dysfunction and diseases of cognitive decline (e.g. Alzheimer’s, Parkinson’s and Huntington's disease). This contrasts with so-called functional amyloids which are non-toxic ordered template structures amenable to applications in tissue engineering. Amyloid fibrils of variable morphology including long and hollow fibres and flattened tube and spiral ribbon-like structures have been used in engineering applications in nano-biology. Protein assemblies based on amyloid core structures display diverse biological functionalities could be applied in futuristic self-assembling biomaterials in nano-electronics. These possibilities have revolutionized the development of next generation computers and biosensors, ultracapacitors, memristors, actuators, molecular switches and could also be used to develop artificial synapses. Amyloid fibril assemblies have also been used in photoelectric and photon capture light harvesting technologies and been applied in innovative nano-photoelectronics and photovoltaics. Hybrid Aβ(16–22)-α-synuclein amyloid fibrils also exhibit light-harvesting and electron-transfer properties. Engineered amyloid assemblies are thus facilitating innovative futuristic advances in nano-technology. Furthermore, with a better understanding of amyloid fibril assembly processes it may be possible to develop therapeutic methods that prevent the toxic build up of this polymer in brain tissues that leads to diseases of cognitive decline. With the ever-expanding prevalence of these diseases in the ageing general global population, there certainly is a clear and present need to find a remedy for these debilitating conditions.

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Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel

Cited by 16 publications

References 125 publications

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy

An Epigenetic Manifestation of Alzheimer's Disease: DNA Methylation

Amyloid, a Jekyll and Hyde Molecule Inducing Neuronal Decline and Cognitive Dysfunction is Also a Unique Molecular Template used in Nano-electronics, Light Capture Photovoltaics, and Biosensors in Neuromorphic Computing.

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