Tauopathy

Ran, Hao; Sang, Tzu-Kang; Chang, Hui-Yun

doi:10.5772/intechopen.73198

Cited by 4 publications

(3 citation statements)

References 162 publications

(259 reference statements)

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“…Tau detachment results in its accumulation in the cytoplasm, followed by its export into the intercellular space and aggregation in neurofibrillary tangles [ 24 ]. The condition characterized by such aggregation is called tauopathy [ 25 ].…”

Section: Role Of Autophagy In Disease Developmentmentioning

confidence: 99%

“…Отсоединение тау-белка приводит к его накоплению в цитоплазме и его последующему экспорту в межклеточное пространство и агрегации в нейрофибриллярные бляшки [24]. Состояние, при котором происходит данная агрегация, получило название таупатия [25].…”

Section: болезнь альцгеймера и роль аутофагии в ее развитииunclassified

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The Role of Autophagy in the Development of Pathological Conditions of the Body

Kench,

Sologova,

Prasolov

et al. 2023

Acta Naturae

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Autophagy is the process of lysosomal elimination of the cell organelles, cytoplasmic sites, and pathogenic microorganisms that enter the cell. This process is associated with both cell death regulation and an increase in cell survival chances. Autophagy is involved in the development of various diseases (Crohn disease, cancer, atherosclerosis, etc.). For these reasons, it is of significant interest to establish the molecular targets involved in autophagy regulation and the factors that mediate its participation in pathogenesis. The review describes the potential molecular mechanisms involved in the regulation of autophagy, its contribution to the vital cell activity in a healthy organism, and pathologies.

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Section: Role Of Autophagy In Disease Developmentmentioning

confidence: 99%

Section: болезнь альцгеймера и роль аутофагии в ее развитииunclassified

The Role of Autophagy in the Development of Pathological Conditions of the Body

Kench,

Sologova,

Prasolov

et al. 2023

Acta Naturae

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“…Tauopathies are a class of heterogeneous neurodegenerative disorders generally characterized by a progressive decline of cognitive functions, change in personality and memory deficit in patients [ 1 , 2 ]. At present, more than twenty neurodegenerative disorders are classified as tauopathies [ 3 , 4 ], the Alzheimer’s Disease (AD) being the most common [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Chemoinformatics Analyses of Tau Ligands Reveal Key Molecular Requirements for the Identification of Potential Drug Candidates against Tauopathies

2021

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Tau is a highly soluble protein mainly localized at a cytoplasmic level in the neuronal cells, which plays a crucial role in the regulation of microtubule dynamic stability. Recent studies have demonstrated that several factors, such as hyperphosphorylation or alterations of Tau metabolism, may contribute to the pathological accumulation of protein aggregates, which can result in neuronal death and the onset of a number of neurological disorders called Tauopathies. At present, there are no available therapeutic remedies able to reduce Tau aggregation, nor are there any structural clues or guidelines for the rational identification of compounds preventing the accumulation of protein aggregates. To help identify the structural properties required for anti-Tau aggregation activity, we performed extensive chemoinformatics analyses on a dataset of Tau ligands reported in ChEMBL. The performed analyses allowed us to identify a set of molecular properties that are in common between known active ligands. Moreover, extensive analyses of the fragment composition of reported ligands led to the identification of chemical moieties and fragment combinations prevalent in the more active compounds. Interestingly, many of these fragments were arranged in recurring frameworks, some of which were clearly present in compounds currently under clinical investigation. This work represents the first in-depth chemoinformatics study of the molecular properties, constituting fragments and similarity profiles, of known Tau aggregation inhibitors. The datasets of compounds employed for the analyses, the identified molecular fragments and their combinations are made publicly available as supplementary material.

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Cleavage of human tau at Asp421 inhibits hyperphosphorylated tau induced pathology in a Drosophila model

Ran

Sun

Shiu

et al. 2020

Sci Rep

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Hyperphosphorylated and truncated tau variants are enriched in neuropathological aggregates in diseases known as tauopathies. However, whether the interaction of these posttranslational modifications affects tau toxicity as a whole remains unresolved. By expressing human tau with disease-related Ser/Thr residues to simulate hyperphosphorylation, we show that despite severe neurodegeneration in full-length tau, with the truncation at Asp421, the toxicity is ameliorated. Cytological and biochemical analyses reveal that hyperphosphorylated full-length tau distributes in the soma, the axon, and the axonal terminal without evident distinction, whereas the Asp421-truncated version is mostly restricted from the axonal terminal. This discrepancy is correlated with the fact that fly expressing hyperphosphorylated full-length tau, but not Asp421-cleaved one, develops axonopathy lesions, including axonal spheroids and aberrant actin accumulations. The reduced presence of hyperphosphorylated tau in the axonal terminal is corroborated with the observation that flies expressing Asp421-truncated variants showed less motor deficit, suggesting synaptic function is preserved. The Asp421 cleavage of tau is a proteolytic product commonly found in the neurofibrillary tangles. Our finding suggests the coordination of different posttranslational modifications on tau may have an unexpected impact on the protein subcellular localization and cytotoxicity, which may be valuable when considering tau for therapeutic purposes.

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Tauopathy

Cited by 4 publications

References 162 publications

The Role of Autophagy in the Development of Pathological Conditions of the Body

The Role of Autophagy in the Development of Pathological Conditions of the Body

Chemoinformatics Analyses of Tau Ligands Reveal Key Molecular Requirements for the Identification of Potential Drug Candidates against Tauopathies

Cleavage of human tau at Asp421 inhibits hyperphosphorylated tau induced pathology in a Drosophila model

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