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The Neurodegenerative Elderly Syndrome (NES) hypothesis: Alzheimer and Parkinson are two faces of the same disease.

ABSTRACT: Increasing evidence suggests that Alzheimer's disease (AD) and Parkinson's disease (PD) share monoamine and alpha-synuclein (αSyn) dysfunctions, often beginning years before clinical manifestations onset. The triggers for these impairments and the causes leading these early neurodegenerative processes to become AD or PD remain unclear. We address these issues by proposing a radically new perspective to frame AD and PD: they are different manifestations of one only disease we call "Neurodegenerative Elderly Syndrome (NES)". NES goes through three phases. The seeding stage, which starts years before clinical signs, and where the part of the brain-body affected by the initial αSyn and monoamine dysfunctions, influences the future possible progression of NES towards PD or AD. The compensatory stage, where the clinical symptoms are still silent thanks to compensatory mechanisms keeping monoamine concentrations homeostasis. The bifurcation stage, where NES becomes AD or PD. We present recent literature supporting NES and discuss how this hypothesis could radically change the comprehension of AD and PD comorbidities and the design of novel system-level diagnostic and therapeutic actions.

SUBMITTER: Caligiore D

PROVIDER: S-EPMC9554826 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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The Neurodegenerative Elderly Syndrome (NES) hypothesis: Alzheimer and Parkinson are two faces of the same disease.

Caligiore Daniele D Giocondo Flora F Silvetti Massimo M

IBRO neuroscience reports 20220926

Increasing evidence suggests that Alzheimer's disease (AD) and Parkinson's disease (PD) share monoamine and alpha-synuclein (αSyn) dysfunctions, often beginning years before clinical manifestations onset. The triggers for these impairments and the causes leading these early neurodegenerative processes to become AD or PD remain unclear. We address these issues by proposing a radically new perspective to frame AD and PD: they are different manifestations of one only disease we call "Neurodegenerat ...[more]

PMID: 36247524

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Project description:Non coding RNAs (ncRNAs) have emerged as regulators of human carcinogenesis by affecting the expression of key tumor suppressor genes and oncogenes. They are divided into short and long ncRNAs, according to their length. Circular RNAs (circRNAs) are included in the second group and were recently discovered as being originated by back-splicing, joining either single or multiple exons, or exons with retained introns. The human Plasmacytoma Variant Translocation 1 (PVT1) gene maps on the long arm of chromosome 8 (8q24) and encodes for 52 ncRNAs variants, including 26 linear and 26 circular isoforms, and 6 microRNAs. PVT1 genomic locus is 54 Kb downstream to MYC and several interactions have been described among these two genes, including a feedback regulatory mechanism. MYC-independent functions of PVT1/circPVT1 have been also reported, especially in the regulation of immune responses. We here review and discuss the role of both PVT1 and circPVT1 in the hematopoietic system. No information is currently available concerning their transforming ability in hematopoietic cells. However, present literature supports their cooperation with a more aggressive and/or undifferentiated cell phenotype, thus contributing to cancer progression. PVT1/circPVT1 upregulation through genomic amplification or rearrangements and/or increased transcription, provides a proliferative advantage to malignant cells in acute myeloid leukemia, acute promyelocytic leukemia, Burkitt lymphoma, multiple myeloma (linear PVT1) and acute lymphoblastic leukemia (circPVT1). In addition, PVT1 and circPVT1 regulate immune responses: the overexpression of the linear form in myeloid derived suppressor cells induced immune tolerance in preclinical tumor models and circPVT1 showed immunosuppressive properties in myeloid and lymphoid cell subsets. Overall, these recent data on PVT1 and circPVT1 functions in hematological malignancies and immune responses reflect two faces of the same coin: involvement in cancer progression by promoting a more aggressive phenotype of malignant cells and negative regulation of the immune system as a novel potential therapy-resistance mechanism.

Dataset Information

The Neurodegenerative Elderly Syndrome (NES) hypothesis: Alzheimer and Parkinson are two faces of the same disease.

Publications

The Neurodegenerative Elderly Syndrome (NES) hypothesis: Alzheimer and Parkinson are two faces of the same disease.

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