Cited by 21Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Novel approaches to increase synaptic resilience as potential treatments for Alzheimer’s disease

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Pham, Andrew Q., Dore, Kim·2023·Seminars in Cell & Developmental Biology

Abstract

A significant proportion of brains with Alzheimer's disease pathology are obtained from patients that were cognitively normal, suggesting that differences within the brains of these individuals made them resilient to the disease. Here, we describe recent approaches that specifically increase synaptic resilience, as loss of synapses is considered to be the first change in the brains of Alzheimer's patients. We start by discussing studies showing benefit from increased expression of neurotrophic factors and protective genes. Methods that effectively make dendritic spines stronger, specifically by acting through actin network proteins, scaffolding proteins and inhibition of phosphatases are described next. Importantly, the therapeutic strategies presented in this review tackle Alzheimer's disease not by targeting plaques and tangles, but instead by making synapses resilient to the pathology associated with Alzheimer's disease, which has tremendous potential.

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Authors
Pham, A. Q., & Dore, K.
Affiliations
University of California San Diego (US)
Venue
Seminars in Cell & Developmental Biology
Publisher
Elsevier BV
Published
2023-04
Volume
139
Pages
84-92
ISSN
1084-9521 (ISSN-L)
OpenAlex
W4221026792
Cited by
21
References
140
Citations by year
2026: 5 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 1
FWCI
0.55
Type
journal article
Language
en
Open access
Locations
  • Seminars in Cell and Developmental Biology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Institute on Aging
  • University of California San Diego (RF1 AG067049)
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, synaptic loss, neurotrophic factors, protective genes, dendritic spines, actin cytoskeleton, scaffold proteins, phosphatase inhibition
MeSH terms
Actins, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Mice, Transgenic, Synapses, Mice

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