Towards a Mechanistic Model of Tau-Mediated Pathology in Tauopathies: What Can We Learn from Cell-Based In Vitro Assays?

Sala-Jarque, Julia; Zimkowska, Karolina; Ávila, Jesús; Ferrer, Isidró; Río, José Antonio del

doi:10.3390/ijms231911527

Cited by 4 publications

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References 150 publications

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“…As one of the causes of primary tauopathies in humans is genetic, with mutations in genes encoding the proteins that promote tau accumulation [ 12 , 27 , 40 ], we analyzed the microtubule-associated protein tau ( MAPT ) gene sequence of all cats. Genomic enrichment, next-generation sequencing, and variant calling identified 3 and 37 private mutations using GATK and VarDict, respectively.…”

Section: Discussionmentioning

confidence: 99%

Primary Feline Tauopathy: Clinical, Morphological, Immunohistochemical, and Genetic Studies

Vidal-Palencia,

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Rebollada-Merino

et al. 2023

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Tauopathies are a group of neurodegenerative diseases characterized by the pathological aggregation of hyperphosphorylated tau in neurons and glia. Primary tauopathies are not uncommon in humans but exceptional in other species. We evaluate the clinical, neuropathological, and genetic alterations related to tau pathology in 16 cats aged from 1 to 21 years with different clinical backgrounds. Interestingly, a 10-year-old female cat presented a six-year progressive history of mental status and gait abnormalities. The imaging study revealed generalized cortical atrophy. Due to the poor prognosis, the cat was euthanatized at the age of ten. Neuropathological lesions were characterized by massive neuronal loss with marked spongiosis and associated moderate reactive gliosis in the parietal cortex, being less severe in other areas of the cerebral cortex, and the loss of Purkinje cells of the cerebellum. Immunohistochemical methods revealed a 4R-tauopathy with granular pre-tangles in neurons and coiled bodies in oligodendrocytes. Deposits were recognized with several phospho-site antibodies (4Rtau, tau5, AT8, PFH, tau-P Thr181, tau-P-Ser 262, tau-P Ser 422) and associated with increased granular expression of active tau kinases (p38-P Thr180/Tyr182 and SAPK/JNK-P Thr138/Thr185). The genetic study revealed well-preserved coding regions of MAPT. No similar alterations related to tau pathology were found in the other 15 cats processed in parallel. To our knowledge, this is the first case reporting a primary 4R-tauopathy with severe cerebral and Purkinje cell degeneration in an adult cat with neurological signs starting at a young age.

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Section: Discussionmentioning

confidence: 99%

Primary Feline Tauopathy: Clinical, Morphological, Immunohistochemical, and Genetic Studies

Vidal-Palencia,

Font,

Rebollada-Merino

et al. 2023

Animals

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“…Understanding such mechanisms is crucial for shedding light on the etiology of human tauopathies and also for identifying novel molecular targets for innovative therapies. In this context, Julia Sala-Jarque and colleagues [7] describe the development of cellular models of tau pathology and the "prion-like" nature of pathological tau. In particular, the authors demonstrate advantages and disadvantages of in vivo rodent models, 2D mammalian immortalized cell lines, microfluidic devices, such as murine neural cells, 2D iPSC-derived neurons, and 3D cerebral organoids.…”

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confidence: 99%