The formation of small aggregates contributes to the neurotoxic effects of tau45-230

Afreen, Sana; Ferreira, Adriana

doi:10.1016/j.neuint.2021.105252

Cited by 5 publications

(4 citation statements)

References 64 publications

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“…In numerous prevalent neurological conditions, fibrillar amyloid-like deposits and tau and α-synuclein co-deposits have been identified ( Elimova et al, 2004 ; Carter, 2006 ). The most significant hazardous aggregation species, as per the new findings, are tiny oligomers ( Afreen and Ferreira, 2022 ). Nübling et al (2012) elucidated molecular crosstalks between distinct aggregation processes implicated in neurodegeneration and presented a novel viewpoint on interconnections among tau phosphorylation, metal ions, and the production of extremely hazardous oligomer species.…”

Section: Impact Of Environmental Toxicants On Neurodegenerative Disor...mentioning

confidence: 76%

Role of Environmental Toxicants on Neurodegenerative Disorders

Nabi

Tabassum

2022

Front. Toxicol.

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Neurodegeneration leads to the loss of structural and functioning components of neurons over time. Various studies have related neurodegeneration to a number of degenerative disorders. Neurological repercussions of neurodegeneration can have severe impacts on the physical and mental health of patients. In the recent past, various neurodegenerative ailments such as Alzheimer’s and Parkinson’s illnesses have received global consideration owing to their global occurrence. Environmental attributes have been regarded as the main contributors to neural dysfunction-related disorders. The majority of neurological diseases are mainly related to prenatal and postnatal exposure to industrially produced environmental toxins. Some neurotoxic metals, like lead (Pb), aluminium (Al), Mercury (Hg), manganese (Mn), cadmium (Cd), and arsenic (As), and also pesticides and metal-based nanoparticles, have been implicated in Parkinson’s and Alzheimer’s disease. The contaminants are known for their ability to produce senile or amyloid plaques and neurofibrillary tangles (NFTs), which are the key features of these neurological dysfunctions. Besides, solvent exposure is also a significant contributor to neurological diseases. This study recapitulates the role of environmental neurotoxins on neurodegeneration with special emphasis on major neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

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Section: Impact Of Environmental Toxicants On Neurodegenerative Disor...mentioning

confidence: 76%

Role of Environmental Toxicants on Neurodegenerative Disorders

Nabi

Tabassum

2022

Front. Toxicol.

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“…NFT). The tau fragment expressed in the tau 45-230 tg mice was shown to aggregate into dimers and small oligomers that are highly toxic and present in AD patient brains 45 . Furthermore, it was shown that in the presence of this fragment full-length tau forms smaller and potentially more toxic aggregates.…”

Section: Resultsmentioning

confidence: 99%

Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging

Paudel,

Jeong,

Martinez

et al. 2024

Nat Commun

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Alzheimer’s disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a cell death mechanism mediated by short (s) RNAs acting through the RNA-induced silencing complex (RISC). DISE is thus a form of RNA interference, in which G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich 6mer seed matches in genes essential for cell survival, resulting in the activation of cell death pathways. Here, using Argonaute precipitation and RNAseq (Ago-RP-Seq), we analyze RISC-bound sRNAs to quantify 6mer seed toxicity in several model systems. In mouse AD models and aging brain, in induced pluripotent stem cell-derived neurons from AD patients, and in cells exposed to Aβ42 oligomers, RISC-bound sRNAs show a shift to more toxic 6mer seeds compared to controls. In contrast, in brains of “SuperAgers”, humans over age 80 who have superior memory performance, RISC-bound sRNAs are shifted to more nontoxic 6mer seeds. Cells depleted of nontoxic sRNAs are sensitized to Aβ42-induced cell death, and reintroducing nontoxic RNAs is protective. Altogether, the correlation between DISE and Aβ42 toxicity suggests that increasing the levels of nontoxic miRNAs in the brain or blocking the activity of toxic RISC-bound sRNAs could ameliorate neurodegeneration.

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“…In vitro, tau45–230 can oligomerize to form heptamers and octamers [ 176 ]. Another study reported that tau45–230 oligomers can be internalized by cultured hippocampal neurons and induce neurosynaptic degeneration through a clathrin-mediated mechanism [ 177 ].…”

Section: Role Of Tau Fragments In Neurodegenerationmentioning

confidence: 99%

Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer’s Disease and Other Tauopathies

Yang,

Shen,

Shen

et al. 2023

Mol Neurobiol

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Tau, a microtubule-associated protein predominantly localized in neuronal axons, plays a crucial role in promoting microtubule assembly, stabilizing their structure, and participating in axonal transport. Perturbations in tau’s structure and function are implicated in the pathogenesis of neurodegenerative diseases collectively known as tauopathies, the most common disorder of which is Alzheimer’s disease (AD). In tauopathies, it has been found that tau has a variety of post-translational modification (PTM) abnormalities and/or tau is cleaved into a variety of fragments by some specific proteolytic enzymes; however, the precise contributions of these abnormal modifications and fragments to disease onset and progression remain incompletely understood. Herein, we provide an overview about the involvement of distinctive abnormal tau PTMs and different tau fragments in the pathogenesis of AD and other tauopathies and discuss the involvement of proteolytic enzymes such as caspases, calpains, and asparagine endopeptidase in mediating tau cleavage while also addressing the intercellular transmission role played by tau. We anticipate that further exploration into PTMs and fragmented forms of tau will yield valuable insights for diagnostic approaches and therapeutic interventions targeting AD and other related disorders.

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The formation of small aggregates contributes to the neurotoxic effects of tau45-230

Cited by 5 publications

References 64 publications

Role of Environmental Toxicants on Neurodegenerative Disorders

Role of Environmental Toxicants on Neurodegenerative Disorders

Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging

Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer’s Disease and Other Tauopathies

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