The DOI matches its Crossref record; 149 of the 150 references it cites were found in a registry or an index.
The molecular bases of Alzheimer’s disease and other neurodegenerative disorders
Open accessAbstract
Alzheimer's disease, the cause of one of the most common types of dementia, is a brain disorder affecting the elderly and is characterized by the formation of two main protein aggregates: senile plaques and neurofibrillary tangles, which are involved in the process leading to progressive neuronal degeneration and death. Neurodegeneration in Alzheimer's disease is a pathologic condition of cells rather than an accelerated way of aging. The senile plaques are generated by a deposition in the human brain of fibrils of the beta-amyloid peptide (Abeta), a fragment derived from the proteolytic processing of the amyloid precursor protein (APP). Tau protein is the major component of paired helical filaments (PHFs), which form a compact filamentous network described as neurofibrillary tangles (NFTs). Experiments with hippocampal cells in culture have indicated a relationship between fibrillary amyloid and the cascade of molecular signals that trigger tau hyperphosphorylations. Two main protein kinases have been shown to be involved in anomalous tau phosphorylations: the cyclin-dependent kinase Cdk5 and glycogen synthase kinase GSK3beta. Cdk5 plays a critical role in brain development and is associated with neurogenesis as revealed by studies in brain cells in culture and neuroblastoma cells. Deregulation of this protein kinase as induced by extracellular amyloid loading results in tau hyperphosphorylations, thus triggering a sequence of molecular events that lead to neuronal degeneration. Inhibitors of Cdk5 and GSK3beta and antisense oligonucleotides exert protection against neuronal death. On the other hand, there is cumulative evidence from studies in cultured brain cells and on brains that oxidative stress constitutes a main factor in the modification of normal signaling pathways in neuronal cells, leading to biochemical and structural abnormalities and neurodegeneration as related to the pathogenesis of Alzheimer's disease. This review is focused on the main protein aggregates responsible for neuronal death in both sporadic and familial forms of Alzheimer's disease, as well as on the alterations in the normal signaling pathways of functional neurons directly involved in neurodegeneration. The analysis is extended to the action of neuroprotective factors including selective inhibitors of tau phosphorylating protein kinases, estrogens, and antioxidants among other molecules that apparently prevent neuronal degeneration.
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“NTFs contain, as their first component, aggregates of the protein tau (τ) in a hyperphosphorylated state.”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [19]
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“in healthy neuronal cells, following consecutive and reversible enzymatic processes of phosphorylation and dephosphorylation, it has the task of assembling and stabilizing microtubules and determining their binding with other components of the cytoskeleton [19,20].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [19]
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Oxidative Stress and the Pathogenesis of Alzheimer's Disease
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Expression of Nrf2 in Neurodegenerative Diseases
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Metadata
- Authors
- Maccioni, R. B., Muñoz, J. P., & Barbeito, L.
- Affiliations
- University of Chile (CL)
- Instituto de Investigaciones Biológicas Clemente Estable (UY)
- Corresponding author
- Maccioni, Ricardo B
- Venue
- Archives of Medical Research
- Publisher
- Elsevier BV
- Published
- 2001-09
- Volume
- 32
- Issue
- 5
- Pages
- 367-381
- ISSN
- 0066-6769 (ISSN-L)
- 0188-4409
- OpenAlex
- W1985122965
- Cited by
- 474
- References
- 150
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 24 · 2023: 8 · 2022: 13 · 2021: 14 · 2020: 17 · 2019: 19 · 2018: 20 · 2017: 28 · 2016: 17 · 2015: 17 · 2014: 19 · 2013: 22 · 2012: 30
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- green
- americanae.aecid.es
- Licence
- Locations
- Archives of Medical Research (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, neurodegeneration, amyloid plaques, neurofibrillary tangles, amyloid-beta, amyloid precursor protein, tau protein, tau hyperphosphorylation, cyclin-dependent kinase 5, GSK3β, oxidative stress, neuronal cell death, neuroprotective factors, estrogen, antioxidants, protein kinase inhibitors, antisense oligonucleotides, dementia
- MeSH terms
- Adult, Aged, alpha-Macroglobulins, Alzheimer Disease, Amino Acid Sequence, Apolipoproteins E, Astrocytes, Calcium, Estrogens, Humans, Membrane Proteins, Memory Disorders, Middle Aged, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Neurotoxins, Nitric Oxide, Parkinson Disease, Protein Processing, Post-Translational, Signal Transduction, Motor Neuron Disease, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Cell Death, Age of Onset, Oxidative Stress, Neurodegenerative Diseases, Caspases, Presenilin-1, Presenilin-2
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