The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivo.

Zhou, Lujia; Barão, Soraia; Laga, Mathias; Bockstael, Katrijn; Borgers, M.; Gijsen, Harry; Annaert, Wim; Moechars, Diederik; Mercken, Marc; Gevaert, Kris; Strooper, Bart De

doi:10.1074/jbc.a112.377465

Cited by 35 publications

(50 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…; Zhou et al . ) has led to important insights into the molecular basis of BACE1‐dependent axon guidance. CHL1 is a type I membrane protein involved in axon outgrowth and neuronal survival (Naus et al .…”

Section: Bace1 Functions In the Cnsmentioning

confidence: 99%

See 1 more Smart Citation

Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects

Vassar

Kuhn

Haass

et al. 2014

Journal of Neurochemistry

289

272

View full text Add to dashboard Cite

The β-site APP cleaving enzymes 1 and 2 (BACE1 and BACE2) were initially identified as transmembrane aspartyl proteases cleaving the amyloid precursor protein (APP). BACE1 is a major drug target for Alzheimer’s disease because BACE1-mediated cleavage of APP is the first step in the generation of the pathogenic amyloid-β peptides. BACE1, which is highly expressed in the nervous system, is also required for myelination by cleaving neuregulin 1. Several recent proteomic and in vivo studies usingBACE1-andBACE2-deficient mice demonstrate a much wider range of physiological substrates and functions for both proteases within and outside of the nervous system. For BACE1 this includes axon guidance, neurogenesis, muscle spindle formation, and neuronal network functions, whereas BACE2 was shown to be involved in pigmentation and pancreatic β-cell function. This review highlights the recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism-based liabilities, in particular for BACE inhibitors in Alzheimer’s disease.

show abstract

Section: Bace1 Functions In the Cnsmentioning

confidence: 99%

“…Zhou et al . () identified 13 substrates from cultured neurons under serum‐ and protein‐free conditions and used differential isotopic labeling of terminal amines and Ɛ‐amines for quantification. In contrast, Kuhn et al .…”

Section: Additional Bace1 Substrates In the Cnsmentioning

confidence: 99%

Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects

Vassar

Kuhn

Haass

et al. 2014

Journal of Neurochemistry

289

272

View full text Add to dashboard Cite

show abstract

“…BACE1 knockout mice exhibit deficits in such brain functions [28,52], and it is extremely well known that AD patients display deficits in such functions as well. Interestingly, at approximately the same time, two separate studies identified two cell-adhesion associated molecules, L1 and CHL1, as BACE1 substrates [54,55]. Interestingly, at approximately the same time, two separate studies identified two cell-adhesion associated molecules, L1 and CHL1, as BACE1 substrates [54,55].…”

Section: Targeting Bace1 Therapeutically -Is It a Good Idea?mentioning

confidence: 90%

Modulation of BACE1 Activity as a Potential Therapeutic Strategy for Treating Alzheimer’s Disease

Klaver

Tesco

2014

Drug Design and Discovery in Alzheimer's Disease

View full text Add to dashboard Cite

“…It is reported that BACE1 cleaves IL-1R2 but the total level of IL-IR2 is unchanged in BACE1 −/− cells [57]. Recently, evidence also suggests that BACE1 cleaves enterokinase and the neural cell adhesion molecules (L1 and CHL1) [58,59]. The broader issue of how many substrates interact with BACE1 is being explored, but research suggests that there are dozens of possibilities.…”

Section: Substrates Of Bace1mentioning

confidence: 99%

β-Secretase: its biology as a therapeutic target in diseases

Wang

Shen

2013

Trends in Pharmacological Sciences

View full text Add to dashboard Cite

β-Secretase (BACE1, β-site APP cleaving enzyme 1) is an aspartic proteinase that has multiple functions in various physiological processes, such as cell differentiation, immunoregulation, and cell death. There is increasing evidence that changes in BACE1 activity are involved in many diseases, such as Alzheimer’s disease (AD), schizophrenia, epileptic behavior, and others. However, a deeper understanding of the molecular biology of BACE1 is necessary for further exploration of cell development, immunological regulation, and disease pathogenesis. Here, we review the molecular and cellular biology of BACE1, including its enzymatic properties, structure, biosynthesis, and physiological functions to provide a new perspective and rational assessment of drugability. Lastly, we discuss proposed strategies to control BACE1 activity for possible therapeutic application.

show abstract

The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivo.

Abstract: Authors are urged to introduce these corrections into any reprints they distribute. Secondary (abstract) services are urged to carry notice of these corrections as prominently as they carried the original abstracts.

Cited by 35 publications

References 0 publications

Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects

Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects

Modulation of BACE1 Activity as a Potential Therapeutic Strategy for Treating Alzheimer’s Disease

β-Secretase: its biology as a therapeutic target in diseases

Contact Info

Product

Resources

About