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Alzheimer’s disease: the future
Published in Howard H. Feldman, Atlas of Alzheimer's Disease, 2007
Joyce Lin H. Yeo, Howard H. Feldman
A seminal pathologic event in Alzheimer’s disease is the misfolding and aggregation of normal amyloid beta peptide into β-sheet-rich oligomers that are neurotoxic and deposit as insoluble senile neuritic plaques in AD brains. Newly engineered synthetic β-sheet breaker peptides bind soluble amyloid and prevent or reverse this abnormal conformational change. Application of these peptides in transgenic mice has been shown to demonstrate a reduction of β-amyloid in mouse brain.37
Biochemical Markers for Alzheimer Disease as Reflection of the Neuropathology in Cerebrospinal Fluid:
Published in Robert E. Becker, Ezio Giacobini, Alzheimer Disease, 2020
C. Bancher, H.M. Wisniewski, P.D. Mehta, K.S. Kim, I. Grundke-Iqbal, K. Iqbal
The above mAb was employed to quantitate beta-peptide immunoreactivity in the CSF of the same 19 patients that had been tested with mAb 5-25 to PHF. Beta-peptide antigen was detected in both the AD patients and the controls. However, the concentrations did not differ significantly between the two groups (Fig. 6). This result is not surprising for the following two reasons. (i) Since the beta-peptide is a fragment of a large precursor molecule, this precursor as well as several of its non- amyloidogenic fragments carries the same epitopes as the beta-peptide and must be expected to react with antibodies raised against this sequence. The amyloid precursor appears to be a normal cellular protein and to have soluble derivatives in the CSF (Weidemann et al. 1989; Palmert et al. 1989; Ghiso et al. 1989). Cross-reactivity arising from these molecules will interfere with reactivity of possible beta-peptide in the CSF, and levels of immunoreactivity may not reflect the amount of amyloid present in the brain. (ii) The total number of NP, and thus the amount of amyloid in the brain, does not correlate well with the presence of dementia and cannot be used as a diagnostic criterion for AD. Non-demented aged individuals as well as aged patients with non-AD dementia but high NP counts may represent false positive samples. However, since the deposition of amyloid has been shown to precede the appearance of PHF in Down syndrome (Wisniewski et al. 1987b; Mann and Esiri 1989), a similar time course must be suspected for AD, and it cannot be ruled out that non-demented individuals with high numbers of NP but no or few PHF are at a preclinical stage of AD. Whether such patients may be identified by high levels of beta-peptide antigens in their CSF is at present unknown.
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].
In vitro neuroprotective effects of farnesene sesquiterpene on alzheimer’s disease model of differentiated neuroblastoma cell line
Published in International Journal of Neuroscience, 2021
Mehmet Enes Arslan, Hasan Türkez, Adil Mardinoğlu
At the beginning of Alzheimer’s disease (AD) symptoms, senile plaques (SPs) occurrence and neurofibrillary tangles (NFTs) accumulation are called to be a triggering element in neurotransmitter systems disturbance. Mainly, the SP generally occurs as a result of amyloid-beta (Aβ) protein accumulation in neurons and glial cells. The Aβ accumulation starts when the enzymes required to degrade of Amyloid Precursor Protein (APP) do not work and cannot metabolize Aβ. This accumulation may lead to many conditions such as oxidative stress, cell membrane disruptions, defects in mitochondrial metabolism, cell cycle defects, protein folding errors, and DNA damage [8]. NFTs occur because of the accumulation of incorrectly phosphorylated tau proteins in the cytoskeleton regions within the cell. These bundles form degenerated damaged neurons by preventing the transmission of different cellular components in the neurons, resulting in the death of neuronal cells [9]. Furthermore, studies claimed that abnormal glycosylation of some AChE forms resulted in increased enzyme activity in Alzheimer’s disease. Also, amyloid-beta peptide accumulation was shown to enhanced the expression of AChE [10]. Thus, common treatments of Alzheimer’s disease generally focus on AChE inhibitors to ameliorate the symptoms.
Multidimensional Studies of Pancratium parvum Dalzell Against Acetylcholinesterase: A Potential Enzyme for Alzheimer’s Management
Published in Journal of the American College of Nutrition, 2020
Devashree N. Patil, Shrirang R. Yadav, Sushama Patil, Vishwas A. Bapat, Jyoti P. Jadhav
Amyloid β protein fragment 1–42 was immobilized by applying the amine coupling method on a CM5 sensor chip with a response of 1500 RU. Plant extracts were passed onto the immobilized sensor chip in consideration with two concs (300, 75 µg). The results showed that P. parvum extract exhibited a maximum affinity (9.5 RU) on immobilized amyloid β protein fragment 1–42 in a conc dependent manner. Affinity studies also prominently showed the good binding ability for P. longiflorum and Pancratium species (KFRI) (Figure 2(b)). Based on these results, it can be assumed that some phytomolecules interacting with beta peptide may be responsible to inhibit amyloid beta aggregation. Other than P. parvum remaining plant extracts exhibited less binding affinity with an immobilized ligand. Also, there were several plant-based derivatives available in the literature quoting appreciable ability of inhibition on amyloid plaques (44).