C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease

Abstract

BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aβ (β‐amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPβ in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment.AimsSeveral studies have demonstrated an elevation in the expression level of C/EBPβ among individuals afflicted with AD. Consequently, this review predominantly delves into the association between C/EBPβ expression and the pathological progression of Alzheimer's disease, elucidating its underlying molecular mechanism, and pointing out the possibility that C/EBPβ can be a new therapeutic target for AD.MethodsA systematic literature search was performed across multiple databases, including PubMed, Google Scholar, and so on, utilizing predetermined keywords and MeSH terms, without temporal constraints. The inclusion criteria encompassed diverse study designs, such as experimental, case–control, and cohort studies, restricted to publications in the English language, while conference abstracts and unpublished sources were excluded.ResultsOverexpression of C/EBPβ exacerbates the pathological features of AD, primarily by promoting neuroinflammation and mediating the transcriptional regulation of key molecular pathways, including δ‐secretase, apolipoprotein E4 (APOE4), acidic leucine‐rich nuclear phosphoprotein‐32A (ANP32A), transient receptor potential channel 1 (TRPC1), and Forkhead BoxO (FOXO).DiscussionThe correlation between overexpression of C/EBPβ and the pathological development of AD, along with its molecular mechanisms, is evident. Investigating the pathways through which C/EBPβ regulates the development of AD reveals numerous multiple vicious cycle pathways exacerbating the pathological progression of the disease. Furthermore, the exacerbation of pathological progression due to C/EBPβ overexpression and its molecular mechanism is not limited to AD but also extends to other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS).ConclusionThe overexpression of C/EBPβ accelerates the irreversible progression of AD pathophysiology. Additionally, C/EBPβ plays a crucial role in mediating multiple pathways linked to AD pathology, some of which engender vicious cycles, leading to the establishment of feedback mechanisms. To sum up, targeting C/EBPβ could hold promise as a therapeutic strategy not only for AD but also for other degenerative diseases.

GSK3: A potential target and pending issues for treatment of Alzheimer's disease

“…It is the foremost cause of dementia, and while it remains a growing concern, the ever‐increasing number of patients coupled with slow drug development has resulted in AD becoming a condition that is among the most destructive, expensive, and burdensome. 13 , 14 For instance, in the United States alone, it has been estimated that the cost of AD was approximately $305 billion in 2020, with around 5.8 million Americans affected. 15 In view of latest statistics, it can be anticipated that the figure of affected individuals is likely to rise to 13.8 million by 2050.…”

“…Supported by characteristic pathological markers including the aggregation of Aβ and the formation of neurofibrillary tangles (NFTs), these factors are believed to be the primary contributors to AD. 13 Furthermore, observations of inflammation, 20 mitochondrial malfunction, oxidative stress, 21 autophagy impairment, 22 gut microbiota deregulation 23 and occurrences of ferroptosis 24 have all been documented in relation to the onset and progression of AD. Above all, AD is a highly intricate neurodegenerative disorder that requires ongoing exploration of therapeutic targets and drug development efforts.…”

“…Above all, AD is a highly intricate neurodegenerative disorder that requires ongoing exploration of therapeutic targets and drug development efforts. 13 , 14…”