2018
DOI: 10.1111/bph.14554
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Amyloid precursor protein‐mediated mitochondrial regulation and Alzheimer's disease

Abstract: Despite clear evidence of a neuroprotective physiological role of amyloid precursor protein (APP) and its non‐amyloidogenic processing products, APP has been investigated mainly in animal and cellular models of amyloid pathology in the context of Alzheimer's disease. The rare familial mutations in APP and presenilin‐1/2, which sometimes drive increased amyloid β (Aβ) production, may have unduly influenced Alzheimer's disease research. APP and its cleavage products play important roles in cellular and mitochond… Show more

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Cited by 29 publications
(18 citation statements)
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References 135 publications
(148 reference statements)
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“…There are different hypotheses about the etiopathogenesis of Alzheimer's disease. The typical accepted hypothesis involves histopathologic alterations of senile plaques, neurofibrillary tangles, and neural cells caused by amyloid precipitation [41].…”
Section: Alzheimer's Diseasementioning
confidence: 99%
“…There are different hypotheses about the etiopathogenesis of Alzheimer's disease. The typical accepted hypothesis involves histopathologic alterations of senile plaques, neurofibrillary tangles, and neural cells caused by amyloid precipitation [41].…”
Section: Alzheimer's Diseasementioning
confidence: 99%
“…Even though strategies to elevate expression or activity of these mechanisms still heavily rely on the amyloid cascade hypothesis, they do provide alternative therapeutic opportunities in dementia and relate to the overall increased interest in proteostatic clearance pathways that are further mentioned below. Better preclinically characterized tool compounds that modulate cellular Aβ and APP levels may also assist researchers such as Lopez Sanchez, van Wijngaarden, and Trounce () and Cecon et al (), providing insights into whether it is the loss of protective non‐amyloidogenic APP fragments or a gain of Aβ toxic function that is more detrimental in AD. Cellular location also appears to be an important factor in pathogenesis—the link between APP or APP‐derived peptides and mitochondrial metabolism remains unclear, despite the mitochondria being a location for APP and Aβ, and energy deficiency a recognized early event in AD progression (Lopez Sanchez et al, ).…”
Section: Progress On Recognized Therapeutic Targetsmentioning
confidence: 99%
“…Better preclinically characterized tool compounds that modulate cellular Aβ and APP levels may also assist researchers such as Lopez Sanchez, van Wijngaarden, and Trounce () and Cecon et al (), providing insights into whether it is the loss of protective non‐amyloidogenic APP fragments or a gain of Aβ toxic function that is more detrimental in AD. Cellular location also appears to be an important factor in pathogenesis—the link between APP or APP‐derived peptides and mitochondrial metabolism remains unclear, despite the mitochondria being a location for APP and Aβ, and energy deficiency a recognized early event in AD progression (Lopez Sanchez et al, ). Previously, the few dementia‐associated therapies aimed at mitochondrial dysfunction have focused on reversing oxidative stress and cell death pathways.…”
Section: Progress On Recognized Therapeutic Targetsmentioning
confidence: 99%
“…However, there is currently no drug that can reverse the mechanisms underlying AD. As most of these single‐targeted medicines are associated with various adverse side effects, it is of great significance to research and develop new drugs for the treatment of AD 6–9 …”
Section: Introductionmentioning
confidence: 99%