PMID- 35923547
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230213
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 14
DP  - 2022
TI  - Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms.
PG  - 903973
LID - 10.3389/fnagi.2022.903973 [doi]
LID - 903973
AB  - Tau is a microtubule-associated protein known to bind and promote assembly of 
      microtubules in neurons under physiological conditions. However, under 
      pathological conditions, aggregation of hyperphosphorylated tau causes neuronal 
      toxicity, neurodegeneration, and resulting tauopathies like Alzheimer's disease 
      (AD). Clinically, patients with tauopathies present with either dementia, 
      movement disorders, or a combination of both. The deposition of 
      hyperphosphorylated tau in the brain is also associated with epilepsy and network 
      hyperexcitability in a variety of neurological diseases. Furthermore, 
      pharmacological and genetic targeting of tau-based mechanisms can have 
      anti-seizure effects. Suppressing tau phosphorylation decreases seizure activity 
      in acquired epilepsy models while reducing or ablating tau attenuates network 
      hyperexcitability in both Alzheimer's and epilepsy models. However, it remains 
      unclear whether tauopathy and epilepsy comorbidities are mediated by convergent 
      mechanisms occurring upstream of epileptogenesis and tau aggregation, by 
      feedforward mechanisms between the two, or simply by coincident processes. In 
      this review, we investigate the relationship between tauopathies and seizure 
      disorders, including temporal lobe epilepsy (TLE), post-traumatic epilepsy (PTE), 
      autism spectrum disorder (ASD), Dravet syndrome, Nodding syndrome, Niemann-Pick 
      type C disease (NPC), Lafora disease, focal cortical dysplasia, and tuberous 
      sclerosis complex. We also explore potential mechanisms implicating the role of 
      tau kinases and phosphatases as well as the mammalian target of rapamycin (mTOR) 
      in the promotion of co-pathology. Understanding the role of these co-pathologies 
      could lead to new insights and therapies targeting both epileptogenic mechanisms 
      and cognitive decline.
CI  - Copyright (c) 2022 Hwang, Vaknalli, Addo-Osafo, Vicente and Vossel.
FAU - Hwang, Kaylin
AU  - Hwang K
AD  - Mary S. Easton Center for Alzheimer's Research and Care, Department of Neurology, 
      David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
FAU - Vaknalli, Rahil N
AU  - Vaknalli RN
AD  - Mary S. Easton Center for Alzheimer's Research and Care, Department of Neurology, 
      David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
FAU - Addo-Osafo, Kwaku
AU  - Addo-Osafo K
AD  - Mary S. Easton Center for Alzheimer's Research and Care, Department of Neurology, 
      David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
FAU - Vicente, Mariane
AU  - Vicente M
AD  - Mary S. Easton Center for Alzheimer's Research and Care, Department of Neurology, 
      David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
FAU - Vossel, Keith
AU  - Vossel K
AD  - Mary S. Easton Center for Alzheimer's Research and Care, Department of Neurology, 
      David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
LA  - eng
GR  - R01 AG058820/AG/NIA NIH HHS/United States
GR  - R56 AG074473/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20220718
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC9340804
OTO - NOTNLM
OT  - cognitive decline
OT  - epilepsy
OT  - hyperexcitability
OT  - hyperphosphorylation of tau
OT  - mTOR
OT  - tau
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/05 06:00
MHDA- 2022/08/05 06:01
PMCR- 2022/01/01
CRDT- 2022/08/04 02:19
PHST- 2022/03/24 00:00 [received]
PHST- 2022/06/22 00:00 [accepted]
PHST- 2022/08/04 02:19 [entrez]
PHST- 2022/08/05 06:00 [pubmed]
PHST- 2022/08/05 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2022.903973 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2022 Jul 18;14:903973. doi: 10.3389/fnagi.2022.903973. 
      eCollection 2022.