The Role of ERK1/2 Pathway in the Pathophysiology of Alzheimer’s Disease: An Overview and Update on New Developments

Khezri, Mohammad Rafi; Yousefi, Keyvan; Esmaeili, Ayda; Ghasemnejad‐Berenji, Morteza

doi:10.1007/s10571-022-01191-x

Cited by 27 publications

(19 citation statements)

References 150 publications

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“…Similarly, retinoic acid may also have a role in γ-secretase activity [ 195 ]. This activity may be primarily affected during the synthesis of γ-secretase, which this process has been known to be inhibited by extracellular signal-regulated kinases (ERKs) [ 196 ] via activation of ERKs and phosphorylation through the mitogen-activated protein kinase cascade [ 197 ]. Let alone, retinoic acid has been experimentally shown to increases ERK phosphorylation in a dose-dependent manner [ 195 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in vitro expression of these agents has also been found to be decrease in exposure to tocopherol derivatives [ 200 ]. Although the current body of literature is limited to transcriptional studies [ 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 ], but does gain support from historical animal models with a broader scope on Vitamin E treatment for AD [ 193 , 194 , 195 , 196 , 197 , 203 , 204 , 205 , 206 , 207 ]. This evidence further justifies the need for greater clinical trial coverage of vitamin E treatment.…”

Section: Discussionmentioning

confidence: 99%

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Amylin and Secretases in the Pathology and Treatment of Alzheimer’s Disease

et al. 2022

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Alzheimer’s disease remains a prevailing neurodegenerative condition which has an array physical, emotional, and financial consequences to patients and society. In the past decade, there has been a greater degree of investigation on therapeutic small peptides. This group of biomolecules have a profile of fundamentally sound characteristics which make them an intriguing area for drug development. Among these biomolecules, there are four modulatory mechanisms of interest in this review: alpha-, beta-, gamma-secretases, and amylin. These protease-based biomolecules all have a contributory role in the amyloid cascade hypothesis. Moreover, the involvement of various biochemical pathways intertwines these peptides such that they have shared regulators (i.e., retinoids). Further clinical and translational investigation must occur to gain a greater understanding of its potential application in patient care. The aim of this narrative review is to evaluate the contemporary literature on these protease biomolecule modulators and determine its utility in the treatment of Alzheimer’s disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Amylin and Secretases in the Pathology and Treatment of Alzheimer’s Disease

et al. 2022

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“…In addition, cleavage of APP by BACE-1 leads to liberate soluble N-terminus of APP and a membrane bound C-terminal fragment (C99). At the second step, C99 fragment is cleaved by γ-secretase which contributes to Aβ release into the extracellular space [35]. The other pathway of APP processing, known as non-Amyloidogenesis pathway, is initiated by α-secretase activity.…”

Section: Adam10 and Aβ In Alzheimer's Diseasementioning

confidence: 99%

Therapeutic potential of ADAM10 modulation in Alzheimer’s disease: a review of the current evidence

2023

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Alzheimer’s disease (AD), the most common neurodegenerative disease worldwide, is caused by loss of neurons and synapses in central nervous system. Several causes for neuronal death in AD have been introduced, the most important of which are extracellular amyloid β (Aβ) accumulation and aggregated tau proteins. Increasing evidence suggest that targeting the process of Aβ production to reduce its deposition can serve as a therapeutic option for AD management. In this regard, therapeutic interventions shown that a disintegrin and metalloproteinase domain-containing protein (ADAM) 10, involved in non-amyloidogenic pathway of amyloid precursor protein processing, is known to be a suitable candidate. Therefore, this review aims to examine the molecular properties of ADAM10, its role in AD, and introduce it as a therapeutic target to reduce the progression of the disease.

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“…These pro-inflammatory cytokines include IL-1α, IL-1β, IL-6, interferon- α (IFN-α), TNF-α and granulocyte-macrophage colony-stimulating factor (GM-CSF) ( Rubio-Perez and Morillas-Ruiz, 2012 ; Babcock et al, 2015 ). Among them, IL-1α and IL-1β can regulate the synthesis and secretion of APP, promote the production of Aβ ( Akama and Van Eldik, 2000 ), and increase the phosphorylation of tau protein through the MAPK-p38 pathway ( Han et al, 2017 ; Khezri et al, 2022 ). IL-6 stimulates astrocyte proliferation ( Lee et al, 2021 ), activates microglia ( West et al, 2022 ), increases APP expression ( Tsatsanis et al, 2021 ), and increases tau phosphorylation through the cdk5/p35 pathway ( Huang et al, 2022 ).…”

Section: Neuroinflammation In Alzheimer’s Diseasementioning

confidence: 99%

The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer’s Disease

Weng

Lai

Wang

et al. 2022

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive dementia. Accumulation of β–amyloid peptide 1–42 and phosphorylation of tau protein in the brain are the two main pathological features of AD. However, comprehensive studies have shown that neuroinflammation also plays a crucial role in the pathogenesis of AD. Neuroinflammation is associated with neuronal death and abnormal protein aggregation and promotes the pathological process of β-amyloid peptide 1–42 and tau protein. The inflammatory components associated with AD include glial cells, complement system, cytokines and chemokines. In recent years, some researchers have focused on exosomes, a type of membrane nano vesicles. Exosomes can transport proteins, lipids, microRNAs and other signaling molecules to participate in a variety of signaling pathways for signal transmission or immune response, affecting the activity of target cells and participating in important pathophysiological processes. Therefore, exosomes play an essential role in intercellular communication and may mediate neuroinflammation to promote the development of AD. This paper reviews the occurrence and development of neuroinflammation and exosomes in AD, providing a deeper understanding of the pathogenesis of AD. Furthermore, the role of exosomes in the pathogenesis and treatment of AD is further described, demonstrating their potential as therapeutic targets for neuroinflammation and AD in the future.

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The Role of ERK1/2 Pathway in the Pathophysiology of Alzheimer’s Disease: An Overview and Update on New Developments

Cited by 27 publications

References 150 publications

Amylin and Secretases in the Pathology and Treatment of Alzheimer’s Disease

Amylin and Secretases in the Pathology and Treatment of Alzheimer’s Disease

Therapeutic potential of ADAM10 modulation in Alzheimer’s disease: a review of the current evidence

The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer’s Disease

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