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Cited by 102Neurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration MechanismsGenetics, Aging, and Longevity in Model Organisms

Mechanisms of neuroplasticity and brain degeneration: strategies for protection during the aging process

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Viel, TaniaAraujo, Toricelli, Mariana, Pereira, ArthurAntonio Ruiz, Souza Abrao, Guilherme, Malerba, HelenaNascimento, Maia, Julia, Buck, HudsonSousa·2021·Neural Regeneration Research
DOI 10.4103/1673-5374.286952PMC PMC7818866
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Abstract

Aging is a dynamic and progressive process that begins at conception and continues until death. This process leads to a decrease in homeostasis and morphological, biochemical and psychological changes, increasing the individual's vulnerability to various diseases. The growth in the number of aging populations has increased the prevalence of chronic degenerative diseases, impairment of the central nervous system and dementias, such as Alzheimer's disease, whose main risk factor is age, leading to an increase of the number of individuals who need daily support for life activities. Some theories about aging suggest it is caused by an increase of cellular senescence and reactive oxygen species, which leads to inflammation, oxidation, cell membrane damage and consequently neuronal death. Also, mitochondrial mutations, which are generated throughout the aging process, can lead to changes in energy production, deficiencies in electron transport and apoptosis induction that can result in decreased function. Additionally, increasing cellular senescence and the release of proinflammatory cytokines can cause irreversible damage to neuronal cells. Recent reports point to the importance of changing lifestyle by increasing physical exercise, improving nutrition and environmental enrichment to activate neuroprotective defense mechanisms. Therefore, this review aims to address the latest information about the different mechanisms related to neuroplasticity and neuronal death and to provide strategies that can improve neuroprotection and decrease the neurodegeneration caused by aging and environmental stressors.

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  • According to the maladaptive synaptoplasticity hypothesis, amyloid plaques, tau pathology, and synaptic loss are not independent triggers but downstream consequences of aberrant plasticity driven by genetic and environmental risk factors.

    “According to this view, the hallmark features of AD, amyloid plaques, tau pathology, and synaptic loss are not independent triggers, but rather downstream consequences of aberrant plasticity driven by genetic and environmental risk factors [80, 81].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [80]

    In “Neuroplasticity and Cell Survival” (page unavailable), the paper says high densities of amyloid plaques induce changes in NMDA receptors involved in synaptic plasticity—the reverse of the claimed direction from aberrant plasticity to plaques. Its introduction mentions genetic and environmental contributions to neurodegenerative disease, but it does not present plaques, tau pathology, and synaptic loss as downstream consequences of aberrant plasticity. (LLM, conf=0.83)

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  • The maladaptive synaptoplasticity hypothesis proposes that the initiating event in AD is an abnormal synaptic plasticity response, whereby excessive or dysfunctional remodeling in evolutionarily vulnerable postsynaptic neurons drives the cascade of pathological changes.

    “The maladaptive synaptoplasticity hypothesis proposes that the initiating event in AD is an abnormal synaptic plasticity response, whereby excessive or dysfunctional remodeling in evolutionarily vulnerable postsynaptic neurons drives the cascade of pathological changes [80, 81].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [80]

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  • A reduction in presynaptic input initiates maladaptive responses that ultimately promote the formation of NFTs.

    “Specifically, a reduction in presynaptic input initiates maladaptive responses that ultimately promote the formation of NFTs.”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [80]

    The Neuroplasticity and Cell Survival section discusses presynaptic signaling, while the Cell senescence, neurodegeneration and neuroprotection section links tau phosphorylation to cellular toxicity. Neither passage says that reduced presynaptic input initiates responses that lead to neurofibrillary tangles. Searches for that causal sequence and for neurofibrillary tangles found no supporting passage in our copy. (LLM, conf=0.72)

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Cited by

Sorted by citations

Authors
Viel, T., Toricelli, M., Pereira, A. R., Souza Abrao, G., Malerba, H., Maia, J., & Buck, H.
Affiliations
Faculdade de Ciências Médicas da Santa Casa de São Paulo (BR)
ORCID
Toricelli, Mariana
Venue
Neural Regeneration Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021
Volume
16
Issue
1
Pages
58
ISSN
1673-5374 (ISSN-L)
DOI
10.4103/1673-5374.286952
PMC
PMC7818866
OpenAlex
W3048379582
Cited by
102
References
13
Citations by year
2026: 7 · 2025: 22 · 2024: 30 · 2023: 15 · 2022: 13 · 2021: 14 · 2020: 1
FWCI
4.21
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Neural Regeneration Research (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
neuroplasticity, brain aging, neurodegeneration, neuroprotection, neuronal cell death, cellular senescence, reactive oxygen species, mitochondrial mutations, neuroinflammation, inflammatory cytokines, Alzheimer's disease, dementia, physical activity, nutrition, environmental enrichment, lifestyle intervention

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