Alternative splicing in aging and Alzheimer's disease: Highlighting the role of tau and estrogen receptor α isoforms in the hypothalamus

Ishunina, Tatjana A.

doi:10.1016/b978-0-12-819973-2.00012-5

Cited by 9 publications

(6 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The human MAPT gene is located on chromosome 17q21 and is organized into 16 exons conventionally numbered as represented in Figure 1 [ 1 , 19 , 20 , 21 ]. Tau belongs to a family of homologous proteins, including MAP2 and MAP4, with 3 or 4 repeated basic microtubule-binding domains (MTBDs) in their carboxy-terminal regions.…”

Section: Mapt Gene Organization and Alternatively Spliced Tr...mentioning

confidence: 99%

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

Corsi

Bombieri

Valenti

2022

IJMS

View full text Add to dashboard Cite

Tau microtubule-associated proteins, encoded by the MAPT gene, are mainly expressed in neurons participating in axonal transport and synaptic plasticity. Six major isoforms differentially expressed during cell development and differentiation are translated by alternative splicing of MAPT transcripts. Alterations in the expression of human Tau isoforms and their aggregation have been linked to several neurodegenerative diseases called tauopathies, including Alzheimer’s disease, progressive supranuclear palsy, Pick’s disease, and frontotemporal dementia with parkinsonism linked to chromosome 17. Great efforts have been dedicated in recent years to shed light on the complex regulatory mechanism of Tau splicing, with a perspective to developing new RNA-based therapies. This review summarizes the most recent contributions to the knowledge of Tau isoform expression and experimental models, highlighting the role of cis-elements and ribonucleoproteins that regulate the alternative splicing of Tau exons.

show abstract

Section: Mapt Gene Organization and Alternatively Spliced Tr...mentioning

confidence: 99%

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

Corsi

Bombieri

Valenti

2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Whether the functions of ERα and ERβ confer neuroprotection is still under investigation. Some studies show ERα is more neuroprotective than ERβ, while others have shown the opposite (Simpkins et al, 2012;Baumgartner and Daniel, 2021;Ishunina, 2021). How these receptors change throughout the life course in the brain in response to changing hormone levels also remains to be elucidated.…”

Section: Potential Mechanisms Driving Sex DI Erences In Alzheimer's D...mentioning

confidence: 99%

Exploring the role of sex differences in Alzheimer's disease pathogenesis in Down syndrome

2022

View full text Add to dashboard Cite

Women are disproportionately affected by Alzheimer's disease (AD), yet little is known about sex-specific effects on the development of AD in the Down syndrome (DS) population. DS is caused by a full or partial triplication of chromosome 21, which harbors the amyloid precursor protein (APP) gene, among others. The majority of people with DS in their early- to mid-40s will accumulate sufficient amyloid-beta (Aβ) in their brains along with neurofibrillary tangles (NFT) for a neuropathological diagnosis of AD, and the triplication of the APP gene is regarded as the main cause. Studies addressing sex differences with age and impact on dementia in people with DS are inconsistent. However, women with DS experience earlier age of onset of menopause, marked by a drop in estrogen, than women without DS. This review focuses on key sex differences observed with age and AD in people with DS and a discussion of possible underlying mechanisms that could be driving or protecting from AD development in DS. Understanding how biological sex influences the brain will lead to development of dedicated therapeutics and interventions to improve the quality of life for people with DS and AD.

show abstract

“…Aberrant AS has been implicated in a wide range of human diseases, including AD ( Koch, 2018 ; Biamonti et al, 2021 ). Specifically, dysregulation of AS has been shown to affect the expression of genes involved in key processes such as synaptic function, neuroinflammation, and tau protein metabolism, which are all critical components of AD pathology ( Ishunina, 2021 ). Despite numerous studies investigating the role of transcriptome in AD, a comprehensive analysis of transcript-level alterations and their biological and clinical implications in AD has been lacking.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive transcript-level analysis reveals transcriptional reprogramming during the progression of Alzheimer’s disease

Wang

et al. 2023

Front. Aging Neurosci.

View full text Add to dashboard Cite

BackgroundAlzheimer’s disease (AD) is a common neurodegenerative disorder that has a multi-step disease progression. Differences between moderate and advanced stages of AD have not yet been fully characterized.Materials and methodsHerein, we performed a transcript-resolution analysis in 454 AD-related samples, including 145 non-demented control, 140 asymptomatic AD (AsymAD), and 169 AD samples. We comparatively characterized the transcriptome dysregulation in AsymAD and AD samples at transcript level.ResultsWe identified 4,056 and 1,200 differentially spliced alternative splicing events (ASEs) that might play roles in the disease progression of AsymAD and AD, respectively. Our further analysis revealed 287 and 222 isoform switching events in AsymAD and AD, respectively. In particular, a total of 163 and 119 transcripts showed increased usage, while 124 and 103 transcripts exhibited decreased usage in AsymAD and AD, respectively. For example, gene APOA2 showed no expression changes between AD and non-demented control samples, but expressed higher proportion of transcript ENST00000367990.3 and lower proportion of transcript ENST00000463812.1 in AD compared to non-demented control samples. Furthermore, we constructed RNA binding protein (RBP)-ASE regulatory networks to reveal potential RBP-mediated isoform switch in AsymAD and AD.ConclusionIn summary, our study provided transcript-resolution insights into the transcriptome disturbance of AsymAD and AD, which will promote the discovery of early diagnosis biomarkers and the development of new therapeutic strategies for patients with AD.

show abstract

Alternative splicing in aging and Alzheimer's disease: Highlighting the role of tau and estrogen receptor α isoforms in the hypothalamus

Cited by 9 publications

References 79 publications

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

Exploring the role of sex differences in Alzheimer's disease pathogenesis in Down syndrome

Comprehensive transcript-level analysis reveals transcriptional reprogramming during the progression of Alzheimer’s disease

Contact Info

Product

Resources

About