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Neurodegeneration in Diabetes Mellitus
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Narsingh Verma, Smriti Rastogi
Amyloid precursor protein is a transmembrane protein whose misprocessing reflects Aβ polypeptide formation. Aβ is one of the major pathological hallmarks accumulating in the extracellular matrix and forms Aβ plaques, which additionally induce inflammation and oxidative stress, reflecting synapse disruption and neurodegeneration.16
Plaques, Tangles and Amyloid:
Published in Robert E. Becker, Ezio Giacobini, Alzheimer Disease, 2020
Robert G. Struble, H. Brent Clark
Even if β-amyloid proves not to be the critical factor in the pathogenesis of AD, it presents an interesting element to study for its own sake. It seems probable that the amyloid precursor protein functions in some important, normal cell-cell interaction, although how is presently unclear. The processes that lead to A4 deposition with subsequent β-amyloid formation in the neuropil in AD probably are of important consequence to the development of AD and may underlie some of the clinical symptomatology. However, we must also be cautious of over-interpreting the importance of β-amyloid in the pathology of AD as this is a relatively new field of study.
Genetic Aspects of Traumatic Brain Injury in Sports
Published in Mark R. Lovell, Ruben J. Echemendia, Jeffrey T. Barth, Michael W. Collins, Traumatic Brain Injury in Sports, 2020
Amyloid precursor protein (APP) is a transmembrane glycoprotein and is the source of the Aβ peptide. It has been generally accepted that APP is upregulated during acute traumatic brain injury (Graham et al., 1995) and in fact may be neuroprotective (Mattson, Cheng, Culwell, 1993). The normal cleavage of APP within the Aβ region by α secretase results in the liberation of secreted forms of APP which have been postulated to protect against hypoglycemic injury by reducing calcium and glutamate neurotoxicity. Graham (Graham et al., 1996) noted an increased expression of APP in the pre α cells of the entorhinal cortex and in areas of axonal injury following TBI. It has been suggested that the long-lasting elevation of APP immunoreactivity is secondary to neuronal damage that stimulates astroglial expression (Siman, Card & Nelson, 1989). In contrast to the concept that APP is neuroprotective, it has been hypthesized that the over-expresion and accumulation of APP in neuronal perikarya in response to TBI, may cause degeneration of CA3 neurons in the hippocampus (Murakami, Yamaki, & Iwamoto, 1998).
Neuroprotective effect of quercetin through targeting key genes involved in aluminum chloride induced Alzheimer’s disease in rats
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Hala A Elreedy, Asmaa M. Elfiky, Asmaa Ahmed Mahmoud, Khadiga S. Ibrahim, Mohamed A Ghazy
Amyloid precursor protein (APP) is a large protein that can have up to 771 amino acids. Non-amyloid products and/or amyloid derivatives of APP are formed by proteolytic action of secretases (α, β and γ) [6]. In the amyloidogenic pathway, soluble amyloid precursor protein β (sAPβ) and C-terminal 99 fragment (CTFβ) were produced from APP by β-secretase cleavage and followed by γ-secretase to generate Aβ peptides [7,8]. Furthermore, the accumulation of these amyloid peptides results in the formation of amyloid-beta fibrils. On the other hand, the non-amyloidogenic pathway, α-secretase cleaves APP to generate the soluble amyloid precursor protein α (sAPP α) and the C83 fragment (CTFα). Then, the sequential degradation of sAPPα by γ-secretase occurred to produce non-amyloidogenic Aβ 17–43 peptides, known as protein 3 (P3) [9].
Beyond the amyloid hypothesis: how current research implicates autoimmunity in Alzheimer’s disease pathogenesis
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Miyo K. Chatanaka, Dorsa Sohaei, Eleftherios P. Diamandis, Ioannis Prassas
Briefly, in the amyloidogenic pathway, the amyloid precursor protein (APP) isoform APP695, which is expressed in neuronal cells, is cleaved by β-secretase (BACE1) and γ-secretase, forming soluble aAPPβ and various-length isoforms of Aβ [54]. This continuous formation of long-length Aβ peptides (Aβ1–40, Aβ1–42) leads to their accumulation in the extracellular space and the development of insoluble plaques. The amyloidogenic pathway is favored when mutations in the APP, presenilin-1 (PS1), and presenilin-2 (PS2) occur, as well as when carrying the risk-conferring apolipoprotein E allele (APOE4). Humans carrying one copy of the APOE4 have a 3-fold increased risk of developing AD, whereas homozygous individuals have a 15-fold increased risk [55]. In addition, tau is a microtubule-associated protein that stabilizes microtubules, protecting them against depolymerization by decreasing the dissociation of tubulin [56]. Tau mutations and hyperphosphorylation damage microtubule function through electrostatic perturbations, disruption of hydrogen bonds and salt bridges, and structural parameter changes, contributing to AD neurodegeneration [57].
Secretory autophagy: a turn key for understanding AMD pathology and developing new therapeutic targets?
Published in Expert Opinion on Therapeutic Targets, 2022
Janusz Blasiak, Kai Kaarniranta
Amyloid beta peptide is a product of the proteolytic cleavage of the amyloid precursor protein (APP). The accumulation of Aβ in the brain plays a role in the pathogenesis of the early stage of Alzheimer’s disease (AD) [30]. The neural retina is the outermost part of the central nervous system (CNS), and AMD is considered as ‘AD of the eye’ or ‘dementia of the eye’ [31,32]. This is justified by the observation that the dysfunction of the H factor of the complement cascade may play a role in the pathogenesis of both AD and AMD [33]. Aβ aggregates were found in drusen deposits [34]. It was shown that rat retinal neurons internalized Aβ 1–42, the most cytotoxic and aggregate-prone member of the Aβ family [35]. Aβ 1–42 affected neuronal microtubule associated protein 2 (MAP2), a regulator of microtubule dynamics in axons and dendrites. Since MAP2 impairment is associated with remodeling of neurons and is reported in AMD retinas, these results may present a molecular mechanism for the involvement of Aβ in AMD pathogenesis. Large drusen under the retina of dry AMD patients may have a high fraction of Aβ, which can underline an association of this form of AMD with observed decline in cognitive functions in AMD patients [32,36]. Dry AMDs and ADs are speculated to belong to a broad spectrum of diseases underlined by the accumulation of Aβ deposits [36].