Cited by 136Neuroinflammation and Neurodegeneration MechanismsCellular transport and secretionAutophagy in Disease and Therapy

The endocytic pathway in microglia during health, aging and Alzheimer’s disease

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Solé-Domènech, Santiago, Cruz, Dana L., Capetillo-Zarate, Estibaliz, Maxfield, Frederick R.·2016·Ageing Research Reviews

Abstract

Microglia, the main phagocytes of the central nervous system (CNS), are involved in the surveillance and maintenance of nervous tissue. During normal tissue homeostasis, microglia migrates within the CNS, phagocytose dead cells and tissue debris, and modulate synapse pruning and spine formation via controlled phagocytosis. In the event of an invasion by a foreign body, microglia are able to phagocytose the invading pathogen and process it proteolytically for antigen presentation. Internalized substrates are incorporated and sorted within the endocytic pathway and thereafter transported via complex vesicular routes. When targeted for degradation, substrates are delivered to acidic late endosomes and lysosomes. In these, the enzymatic degradation relies on pH and enzyme content. Endocytosis, sorting, transport, compartment acidification and degradation are regulated by complex signaling mechanisms, and these may be altered during aging and pathology. In this review, we discuss the endocytic pathway in microglia, with insight into the mechanisms controlling lysosomal biogenesis and pH regulation. We also discuss microglial lysosome function associated with Alzheimer's disease (AD) and the mechanisms of amyloid-beta (Aβ) internalization and degradation. Finally, we explore some therapies currently being investigated to treat AD and their effects on microglial response to Aβ, with insight in those involving enhancement of lysosomal function.

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Crossref · 10.1016/j.arr.2016.07.002

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  1. Lewis WH Pinocytosis Bulletin of the Johns Hopkins Hospital 1931 49 17 27

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Authors
Solé-Domènech, S., Cruz, D. L., Capetillo-Zarate, E., & Maxfield, F. R.
Affiliations
Weill Cornell Medicine (US)
Corresponding author
Maxfield, Frederick R.
Venue
Ageing Research Reviews
Publisher
Elsevier BV
Published
2016-12
Volume
32
Pages
89-103
ISSN
1568-1637 (ISSN-L)
OpenAlex
W2465699308
Cited by
133
References
218
Citations by year
2026: 12 · 2025: 13 · 2024: 23 · 2023: 15 · 2022: 17 · 2021: 14 · 2020: 12 · 2019: 12 · 2018: 5 · 2017: 9 · 2016: 1
FWCI
0.79
Type
journal article
Language
en
Open access
Locations
  • Ageing Research Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
Swedish Research Council (637-2013-503)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
microglia, endocytic pathway, lysosomal biogenesis, Alzheimer's disease, amyloid beta degradation, aging, phagocytosis, antigen presentation, late endosomes, lysosomal storage disease, Alzheimer's disease therapeutics
MeSH terms
Aging, Alzheimer Disease, Animals, Humans, Lysosomes, Phagocytosis, Signal Transduction, Amyloid beta-Peptides, Microglia

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