Deciphering an interplay of proteins associated with amyloid β 1-42 peptide and molecular mechanisms of Alzheimer’s disease

Abstract

<jats:title>Abstract</jats:title><jats:p>Extracellular and intracellular accumulation of amyloid beta 1-42 peptide in different states of aggregation has been involved in the development and progression of Alzheimer’s disease. However, the precise mechanisms involved in amyloid beta peptide neurotoxicity have not been fully understood. There exists a wide variety of studies demonstrating the binding of amyloid beta peptide to a great variety of macromolecules and that such associations affect the cellular functions. This type of association involves proteins and receptors anchored to the plasma membrane of neurons or immune cells of the central nervous system as well as intracellular proteins that can alter intracellular transport, activate signaling pathways or affect proper mitochondrial function. In this review, we present some examples of such associations and the role played by these interactions, which are generally involved in the pathological progression of Alzheimer’s disease.</jats:p>

Structural Changes of Amyloid Beta in Hippocampus of Rats Exposed to Ozone: A Raman Spectroscopy Study

“…Using this model in healthy rats, we have demonstrated that, without any other additional factors, oxidative stress by itself can produce damage and death cell along with the formation of Aβ 1–42, similar to what happens in AD patients (Rivas Arancibia et al, 2011; Hernández-Zimbrón and Rivas-Arancibia, 2014). In addition, ozone exposure also leads to a deficit in the learning and memory processes as well as motor and behavioral impairment in rats (Rivas-Arancibia et al, 1998; Dorado-Martínez et al, 2001).…”

“…The peptide Aβ is generated by the cleavage of the amyloid precursor protein (APP) with the aid of α- and β-enzymes and γ-secretase (Hernández-Zimbrón and Rivas-Arancibia, 2014). The breakdown of APP occurs in two pathways: the non-amyloidogenic and amyloidogenic one.…”

Markers of Alzheimer’s Disease in Primary Visual Cortex in Normal Aging in Mice

“…The A β 42 peptide is the pathological hallmark of AD produced by the sequential cleavage of APP by β -secretase and the gamma-secretase complex. In contrast, the activation of ∂ -secretase leads to nonamyloidogenic processing of APP and the generation of truncated nontoxic sAPPa fragments [ 5 , 22 , 23 ]. Neurofibrillary tangles formed by the pathological hyperphosphorylation of Tau protein, an associated-microtubule protein that helps to stabilize microtubules, are the other AD hallmark.…”

“…Different risk factors have been associated with the development of AD, such as environmental, dietary, and pathological factors, altered glucose metabolism, chronic inflammation, gender, and oxidative stress. Nevertheless, age continues to be the main risk factor for AD, although early-onset disease can occur before the age of 60 years [ 4 , 5 ].…”

“…The production of A β , a critical event in AD, results from the cleavage of the amyloid precursor protein (APP), whose levels are high in AD. This peptide is toxic and induces several detrimental effects on cells, like cell membrane disruption, excessive production of reactive oxygen species, interactions with several proteins that affect their normal function, synaptic failure, chronic local inflammation, glial hyperactivity, and cell death [ 8 ]. These changes have been studied and identified mainly in brain areas such as entorhinal, prefrontal, and visual cortices, hippocampus, and olfactory bulb.…”