MAP2 caps tau fibrils and inhibits aggregation

Holden, Michael R.; Krzesinski, Brad J.; Weismiller, Hilary A.; Shady, Justin R.; Margittai, Martin

doi:10.1016/j.jbc.2023.104891

Cited by 5 publications

(3 citation statements)

References 76 publications

(95 reference statements)

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“…Thus, a decrease in the expression of neuronal genes (e.g. Map2, Camk4, Lamp5) directly indicated the development of Alzheimer's-type neurodegeneration [97,147]. Dysregulation of the Ap2a2 and Efr3a genes observed in OBX mice and characteristic of animal models of AD is often associated with neuro brillary tangles [101] and inhibition of hippocampal neurogenesis characteristic for AD [100].…”

Section: Discussionmentioning

confidence: 99%

“…When analyzing neuronal genes, we demonstrated that Map2, Camk4, and Lamp5 genes drastically reduced their expression in OBX mice, which according to the literature, is characteristic for AD [94][95][96][97]. The Arpp21 gene, which greatly decreases its expression in hippocampal neurons, is directly associated with a reduced dopamine receptor activation [98].…”

Section: Apoptosis and Ferroptosismentioning

confidence: 99%

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A mouse model of sporadic Alzheimer’s disease with elements of major depression

Bobkova,

Chuvakova,

Kovalev

et al. 2024

Preprint

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Animals after bulbectomy are often used as a model of major depression or sporadicAlzheimer’s disease and, hence, the status of this model is still disputable. To elucidate the nature of alterations in the expression of the genome after the operation we analyzed transcriptomes (RNA-seq data) of the cortex, hippocampus, and cerebellum of olfactory bulbectomized (OBX) mice. Analysis of the functional significance of genes in the brain of OBX mice indicates that the balance of the GABA/glutamatergic systems is disturbed with hyperactivation of the latter in the hippocampus leading to the development of excitotoxicity and induction of apoptosis on the background of severe mitochondrial dysfunction and astrogliosis. On top of this, the synthesis of neurotrophic factors decreases leading to the disruption of the cytoskeleton of neurons, an increase in the level of intracellular calcium, and activation of tau protein hyperphosphorylation and beta-amyloid depositions. Moreover, the acetylcholinergic system is deficient in the background of hyperactivation of acetylcholinesterase. Importantly, the activity of the dopaminergic, endorphin, and opiate systems in OBX mice decreases leading to hormonal dysfunction. Genes responsible for the regulation of circadian rhythms, cell migration, and impaired innate immunity are activated in OBX animals. All this takes place on the background of drastic down-regulation of ribosomal protein genes in the brain. The obtained results indicate that OBX mice represent a model of Alzheimer's disease with elements of major depression. This model can be tentatively attributed to AD subtype B2 in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Apoptosis and Ferroptosismentioning

confidence: 99%

A mouse model of sporadic Alzheimer’s disease with elements of major depression

Bobkova,

Chuvakova,

Kovalev

et al. 2024

Preprint

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“…MAP2 plays a key role in neurite and synapse growth and function, and its aberrant phosphorylation is associated with neuropsychiatric and neurodegenerative disorders ( Grubisha et al, 2021 ; DeGiosio et al, 2022 ). Dysregulation of MAP2 is associated with tauopathies, given that MAP2 shares sequences homology with tau and can inhibit its aggregation by binding to the ends of the tau fibrils ( Zhang and Dong, 2012 ; Holden et al, 2023 ).…”

Section: Rna Modificationsmentioning

confidence: 99%

Epigenetic modifications of DNA and RNA in Alzheimer’s disease

Martinez-Feduchi,

Jin,

Yao

2024

Front. Mol. Neurosci.

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Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the most common form of dementia. There are two main types of AD: familial and sporadic. Familial AD is linked to mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2). On the other hand, sporadic AD is the more common form of the disease and has genetic, epigenetic, and environmental components that influence disease onset and progression. Investigating the epigenetic mechanisms associated with AD is essential for increasing understanding of pathology and identifying biomarkers for diagnosis and treatment. Chemical covalent modifications on DNA and RNA can epigenetically regulate gene expression at transcriptional and post-transcriptional levels and play protective or pathological roles in AD and other neurodegenerative diseases.

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