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Cited by 27Alzheimer's disease research and treatmentsCellular transport and secretionProtein Kinase Regulation and GTPase Signaling

A possible role of myristoylated alanine-rich C kinase substrate in endocytic pathway of Alzheimer’s disease

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Su, Rui, Han, Zhen-Yun, Fan, Ji-Ping, Zhang, Yun-Ling·2010·Neuroscience Bulletin
DOI 10.1007/s12264-010-0131-0PMC PMC5552570
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Abstract

It is believed that amyloid-beta peptide (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD). Thus, the process of amyloid precursor protein (APP) cleavage is a key event and has raised much attention in the field of AD research. It is proposed that APP, beta- and gamma-secretases are all located on the lipid raft, and the meeting of them is an indispensable step for Abeta generation. Endocytosis can lead to clustering of APP, beta- and gamma-secretases from separate smaller lipid rafts into a larger one. On the other hand, for myristoylated alanine-rich C kinase substrate (MARCKS), phosphorylation by protein kinase C (PKC) or interaction with Ca(2+) can lead to its release from membrane into cytoplasm. This process induces the release of actins and phosphatidylinositol 4, 5-bisphosphate (PIP2), which are important factors for endocytosis. Thus, the present review proposes that MARCKS may be implicated in Abeta generation, by modulating free PIP2 level and actin movement, causing endocytosis.

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  • The phosphorylation level of MARCKS is associated with Aβ biogenesis and neuron degeneration.

    “MARCKS is the main substrate for PKC, and the phosphorylation level of MARCKS is associated with Aβ biogenesis and neuron degeneration. 53 , 54 , 73”

    From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [73]

    Section 6 says PKC phosphorylation causes MARCKS to move from the membrane, and the figure in Section 8 proposes that this movement can promote endocytosis and Aβ production. The paper does not establish an association between MARCKS phosphorylation levels and neuronal degeneration; its proposed link to Aβ production is also not a measured association. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • MARCKS is the main substrate for PKC.

    “MARCKS is the main substrate for PKC, and the phosphorylation level of MARCKS is associated with Aβ biogenesis and neuron degeneration. 53 , 54 , 73”

    From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [73]

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Cited by

Sorted by citations

Authors
Su, R., Han, Z.-Y., Fan, J.-P., & Zhang, Y.-L.
Affiliations
  • China Academy of Chinese Medical Sciences (CN)
  • Beijing University of Chinese Medicine (CN)
Venue
Neuroscience Bulletin
Publisher
Springer Science and Business Media LLC
Published
2010-08
Volume
26
Issue
4
Pages
338-344
ISSN
  • 1995-8218 (ISSN-L)
  • 1673-7067
DOI
10.1007/s12264-010-0131-0
PMC
PMC5552570
OpenAlex
W2109721379
Cited by
27
References
3
Citations by year
2026: 1 · 2025: 3 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 2
FWCI
0.06
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuroscience Bulletin (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
MARCKS, Alzheimer's disease, amyloid-beta production, amyloid precursor protein, endocytosis, lipid rafts, beta-secretase, gamma-secretase, protein kinase C, phosphatidylinositol 4,5-bisphosphate, actin, APP cleavage
MeSH terms
Myristoylated Alanine-Rich C Kinase Substrate, Alzheimer Disease, Animals, Endocytosis, Humans, Membrane Proteins, Models, Biological, Membrane Microdomains, Intracellular Signaling Peptides and Proteins

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