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Cancer and Alzheimer’s disease inverse relationship: an age-associated diverging derailment of shared pathways
Abstract
Several epidemiological studies show an inverse association between cancer and Alzheimer's disease (AD). It is debated whether this association is the consequence of biological mechanisms shared by both these conditions or may be related to the pharmacological treatments carried out on the patients. The latter hypothesis, however, is not sustained by the available evidence. Hence, the focus of this review is to analyze common biological mechanisms for both cancer and AD and to build up a biological theory useful to explain the inverse correlation between AD and cancer. The review proposes a hypothesis, according to which several molecular players, prominently PIN1 and p53, have been investigated and considered involved in complex molecular interactions putatively associated with the inverse correlation. On the other hand, p53 involvement in both diseases seems to be a consequence of the aberrant activation of other proteins. Instead, PIN1 may be identified as a novel key regulator at the crossroad between cancer and AD. PIN1 is a peptidyl-prolyl cis-trans isomerase that catalyzes the cis-trans isomerization, thus regulating the conformation of different protein substrates after phosphorylation and modulating protein function. In particular, trans-conformations of Amyloid Precursor Protein (APP) and tau are functional and "healthy", while cis-conformations, triggered after phosphorylation, are pathogenic. As an example, PIN1 accelerates APP cis-to-trans isomerization thus favo…
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“Alzheimer’s disease (AD) patients have a decreased incidence of cancer.”
From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [2]
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Metadata
- Authors
- Lanni, C., Masi, M., Racchi, M., & Govoni, S.
- Affiliations
- University of Pavia (IT)
- Corresponding author
- Govoni, Stefano
- Venue
- Molecular Psychiatry
- Published
- 2020-05-07
- Volume
- 26
- Issue
- 1
- Pages
- 280-295
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W3022858905
- Cited by
- 130
- References
- 212
- Citations by year
- 2026: 20 · 2025: 19 · 2024: 26 · 2023: 17 · 2022: 27 · 2021: 15 · 2020: 5
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, cancer, inverse association, Pin1, peptidyl-prolyl isomerase, p53, amyloid precursor protein, tau hyperphosphorylation, non-amyloidogenic pathway, amyloidogenic pathway, mild cognitive impairment, age of onset, cancer risk, neurodegenerative dementia
- MeSH terms
- NIMA-Interacting Peptidylprolyl Isomerase, Aging, Alzheimer Disease, Humans, Neoplasms, Phosphorylation, Tumor Suppressor Protein p53, Amyloid beta-Protein Precursor, Peptidylprolyl Isomerase
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