The Alzheimer’s Disease–Associated Protein BACE1 Modulates T Cell Activation and Th17 Function

Hernández-Mir, Gerard; Raphael, Itay; Revu, Shankar; Poholek, Catherine H.; Avery, Lyndsay; Hawse, William F.; Kane, Larry; McGeachy, Mandy J.

doi:10.4049/jimmunol.1800363

Cited by 13 publications

(13 citation statements)

References 69 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surprisingly, recent studies identified that CD4+ T cells highly expressed BACE1, and BACE1 mediated T-cell activation in the EAE and AD mouse model (Dai et al, 2021;Hernandez-Mir et al, 2019).…”

Section: T-cell Function Is Associated With β-Secretasementioning

confidence: 99%

Insights into T‐cell dysfunction in Alzheimer's disease

Dai

Shen

2021

Aging Cell

View full text Add to dashboard Cite

show abstract

Section: T-cell Function Is Associated With β-Secretasementioning

confidence: 99%

Insights into T‐cell dysfunction in Alzheimer's disease

Dai

Shen

2021

Aging Cell

View full text Add to dashboard Cite

show abstract

“…BACE1 has been shown to be important in Th17 differentiation 158 . BACE1 expression is upregulated in macrophage foam cell regions of atherosclerotic plaques 141 .…”

Section: Bace1 In Immune Functionmentioning

confidence: 99%

BACE1: More than just a β‐secretase

et al. 2022

View full text Add to dashboard Cite

Summary β‐site amyloid precursor protein cleaving enzyme‐1 (BACE1) research has historically focused on its actions as the β‐secretase responsible for the production of β‐amyloid beta, observed in Alzheimer's disease. Although the greatest expression of BACE1 is found in the brain, BACE1 mRNA and protein is also found in many cell types including pancreatic β‐cells, adipocytes, hepatocytes, and vascular cells. Pathologically elevated BACE1 expression in these cells has been implicated in the development of metabolic diseases, including type 2 diabetes, obesity, and cardiovascular disease. In this review, we examine key questions surrounding the BACE1 literature, including how is BACE1 regulated and how dysregulation may occur in disease, and understand how BACE1 regulates metabolism via cleavage of a myriad of substrates. The phenotype of the BACE1 knockout mice models, including reduced weight gain, increased energy expenditure, and enhanced leptin signaling, proposes a physiological role of BACE1 in regulating energy metabolism and homeostasis. Taken together with the weight loss observed with BACE1 inhibitors in clinical trials, these data highlight a novel role for BACE1 in regulation of metabolic physiology. Finally, this review aims to examine the possibility that BACE1 inhibitors could provide a innovative treatment for obesity and its comorbidities.

show abstract

“…BACE1 is a transmembrane asparty1 protease that plays a role in forming plaques in AD (Vassar, 2004 ). BACE1-deficient T cells have reduced IL-17A expression under Th17 conditions in AD mouse models (Hernandez-Mir et al, 2019 ). However, the effect of IL-17A on the pathogenesis of AD is controversial.…”

Section: Role Of Il-17a In Neurodegenerative Diseasesmentioning

confidence: 99%

Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases

Chen

Liu

Zhong

2020

Front. Aging Neurosci.

110

View full text Add to dashboard Cite

Neurodegenerative diseases are characterized by the loss of neurons and/or myelin sheath, which deteriorate over time and cause dysfunction. Interleukin 17A is the signature cytokine of a subset of CD4 + helper T cells known as Th17 cells, and the IL-17 cytokine family contains six cytokines and five receptors. Recently, several studies have suggested a pivotal role for the interleukin-17A (IL-17A) cytokine family in human inflammatory or autoimmune diseases and neurodegenerative diseases, including psoriasis, rheumatoid arthritis (RA), Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and glaucoma. Studies in recent years have shown that the mechanism of action of IL-17A is more subtle than simply causing inflammation. Although the specific mechanism of IL-17A in neurodegenerative diseases is still controversial, it is generally accepted now that IL-17A causes diseases by activating glial cells. In this review article, we will focus on the function of IL-17A, in particular the proposed roles of IL-17A, in the pathogenesis of neurodegenerative diseases.

show abstract

The Alzheimer’s Disease–Associated Protein BACE1 Modulates T Cell Activation and Th17 Function

Cited by 13 publications

References 69 publications

Insights into T‐cell dysfunction in Alzheimer's disease

Insights into T‐cell dysfunction in Alzheimer's disease

BACE1: More than just a β‐secretase

Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases

Contact Info

Product

Resources

About