Targeting Tau to Treat Clinical Features of Huntington's Disease

Masnata, Maria; Salem, Shireen; Jacquet, Aurélie de Rus; Anwer, Mehwish; Cicchetti, Francesca

doi:10.3389/fneur.2020.580732

Cited by 15 publications

(19 citation statements)

References 272 publications

(290 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are consistent with the specific effect of the CP13 antibody on phosphorylation at S202. Overall, these findings confirm previous observations of tau hyperphosphorylation in a number of brain regions implicated in HD pathology 10 and suggest that immunotherapies can target and reduce tau phosphorylation in the CNS, thereby improving tau-associated behavioral phenotypes (Figure S4).…”

Section: Cp13 Treatment Reduces Tau Phosphorylation In Brain Structur...supporting

confidence: 89%

“…Finally, we analyzed tau phosphorylation in the striatum, the most affected brain region in HD pathology. 10,38 We observed that striatal tissue isolated from zQ175 mice expressed significantly greater levels of pS199 tau compared with WT mice, but antibody injections did not alter phosphorylated tau levels at any of the three analyzed residues (i.e., pS199, pS202, and pS396) in either genotype (Figures 2K-2O). Together, these observations suggest that CP13 specifically targets pS202 tau in zQ175 mice, particularly where levels are elevated and that there is no correlation between pS199, pS202, and pS396 levels following antibody treatment.…”

Section: Cp13 Treatment Reduces Tau Phosphorylation In Brain Structur...mentioning

confidence: 86%

“…[4][5][6][7][8] In addition to accumulation of mHTT, cardinal features of tauopathies, namely misfolding, hyperphosphorylation and aggregation of the tau protein into neurofibrillary tangles (NFTs) and neuropil threads (NTs), have been described in the brains of HD patients. 9,10 Tau is primarily expressed in neurons 11 and is involved in essential cellular processes, such as microtubule stability, neurite outgrowth, axonal transport and synaptic plasticity. [12][13][14] Post-translational modifications are key molecular mechanisms responsible for regulating these activities and include phosphorylation and dephosphorylation at multiple residues.…”

Section: Introductionmentioning

confidence: 99%

“…19,27 There is compelling evidence to suggest that HD may be a secondary tauopathy, urging the evaluation of tau's contribution to behavioral and molecular signatures of this neurodegenerative disorder. Immunotherapies, i.e., harnessing the immune system to clear pathological proteins, can efficiently decrease phosphorylated tau levels in animal models of tauopathies, 10,28 suggesting that such approach could be used in HD to untangle the contribution of tau pathology to disease progression. Some studies have now reported that injection of antiphosphorylated tau antibodies into animal models of tauopathy is associated with improved behavioral outcomes and favorable toxicology and safety profiles.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Passive immunization against phosphorylated tau improves features of Huntington's disease pathology

et al. 2022

Self Cite

View full text Add to dashboard Cite

Section: Cp13 Treatment Reduces Tau Phosphorylation In Brain Structur...supporting

confidence: 89%

Section: Cp13 Treatment Reduces Tau Phosphorylation In Brain Structur...mentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Passive immunization against phosphorylated tau improves features of Huntington's disease pathology

et al. 2022

Self Cite

View full text Add to dashboard Cite

“…Additionally, and as a result of splicing alterations, the expression levels of specific Tau isoforms are changed in HD brain tissue causing disruption of the nuclear membrane [ 97 , 98 ]. Based on the documented Tau pathology in HD several investigators have referred to HD as a tauopathy, placing it in the same disease category as AD [ 99 , 100 , 101 , 102 ].…”

Section: The Diseasesmentioning

confidence: 99%

When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer’s and Huntington’s Disease

D’Mello¹

2021

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a mostly sporadic brain disorder characterized by cognitive decline resulting from selective neurodegeneration in the hippocampus and cerebral cortex whereas Huntington’s disease (HD) is a monogenic inherited disorder characterized by motor abnormalities and psychiatric disturbances resulting from selective neurodegeneration in the striatum. Although there have been numerous clinical trials for these diseases, they have been unsuccessful. Research conducted over the past three decades by a large number of laboratories has demonstrated that abnormal actions of common kinases play a key role in the pathogenesis of both AD and HD as well as several other neurodegenerative diseases. Prominent among these kinases are glycogen synthase kinase (GSK3), p38 mitogen-activated protein kinase (MAPK) and some of the cyclin-dependent kinases (CDKs). After a brief summary of the molecular and cell biology of AD and HD this review covers what is known about the role of these three groups of kinases in the brain and in the pathogenesis of the two neurodegenerative disorders. The potential of targeting GSK3, p38 MAPK and CDKS as effective therapeutics is also discussed as is a brief discussion on the utilization of recently developed drugs that simultaneously target two or all three of these groups of kinases. Multi-kinase inhibitors either by themselves or in combination with strategies currently being used such as immunotherapy or secretase inhibitors for AD and knockdown for HD could represent a more effective therapeutic approach for these fatal neurodegenerative diseases.

show abstract

Genetic forms of tauopathies: inherited causes and implications of Alzheimer’s disease-like TAU pathology in primary and secondary tauopathies

Langerscheidt,

Wied,

Al Kabbani

et al. 2024

J Neurol

View full text Add to dashboard Cite

Tauopathies are a heterogeneous group of neurologic diseases characterized by pathological axodendritic distribution, ectopic expression, and/or phosphorylation and aggregation of the microtubule-associated protein TAU, encoded by the gene MAPT. Neuronal dysfunction, dementia, and neurodegeneration are common features of these often detrimental diseases. A neurodegenerative disease is considered a primary tauopathy when MAPT mutations/haplotypes are its primary cause and/or TAU is the main pathological feature. In case TAU pathology is observed but superimposed by another pathological hallmark, the condition is classified as a secondary tauopathy. In some tauopathies (e.g. MAPT-associated frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Alzheimer's disease (AD)) TAU is recognized as a significant pathogenic driver of the disease. In many secondary tauopathies, including Parkinson's disease (PD) and Huntington's disease (HD), TAU is suggested to contribute to the development of dementia, but in others (e.g. Niemann-Pick disease (NPC)) TAU may only be a bystander. The genetic and pathological mechanisms underlying TAU pathology are often not fully understood. In this review, the genetic predispositions and variants associated with both primary and secondary tauopathies are examined in detail, assessing evidence for the role of TAU in these conditions. We highlight less common genetic forms of tauopathies to increase awareness for these disorders and the involvement of TAU in their pathology. This approach not only contributes to a deeper understanding of these conditions but may also lay the groundwork for potential TAU-based therapeutic interventions for various tauopathies.

show abstract

Targeting Tau to Treat Clinical Features of Huntington's Disease

Cited by 15 publications

References 272 publications

Passive immunization against phosphorylated tau improves features of Huntington's disease pathology

Passive immunization against phosphorylated tau improves features of Huntington's disease pathology

When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer’s and Huntington’s Disease

Genetic forms of tauopathies: inherited causes and implications of Alzheimer’s disease-like TAU pathology in primary and secondary tauopathies

Contact Info

Product

Resources

About