2. Introduction
Tauopathies are neurodegenerative diseases that
are pathologically characterized by abnormal tau
aggregates in neurons and glial cells.
Responsible for the majority of dementias
worldwide, including Alzheimer’s disease (AD).
Heterogenous clinical and phenotypes.
Chung, D. eun C., Roemer, S., Petrucelli, L., Dickson, D.W., 2021. Cellular and pathological heterogeneity of primary tauopathies. Mol Neurodegener.
https://doi.org/10.1186/s13024-021-00476-x
3. The Tau
Microtubules are tubulin polymers that are necessary
for cell structure and function.
Tau- for tubulin associated unit- is one of the most
abundant of several microtubule associated proteins
(MAP) found in the nervous system
Tau functions:
- Catalyzes microtubule polymerization, promoting
cytoskeleton structure and axonal transport.
- Signal transduction, DNA/RNA protection, and
regulation of synaptic function.
Weingarten, M.D., Lockwood, A.H., Hwo, S.Y., Kirschner, M.W., 1975. A protein factor essential for microtubule assembly. Proc Natl Acad Sci U S A 72, 1858–62.
https://doi.org/10.1073/pnas.72.5.1858
Catarina Silva, M., Haggarty, S.J., 2020. Tauopathies: Deciphering disease mechanisms to develop effective therapies. Int J Mol Sci.
https://doi.org/10.3390/ijms21238948
4. The Pathological Tau
Kosik, K.S., Joachim, C.L., Selkoe, D.J., 1986. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease.
Proceedings of the National Academy of Sciences 83, 4044–4048. https://doi.org/10.1073/pnas.83.11.4044
7. 4-repeat Tauopathies
Progressive supranuclear palsy
Corticobasal degeneration
Argyrophilic grain disease
Glial globular tauopathy
A group of neurodegenerative diseases defined by cytoplasmic inclusions
predominantly composed of tau protein isoforms with four microtubule-
binding domains
Roesler TW, Marvian AT, Brendel M, Nykaenen NP, Hoellerhage M, Schwarz SC, Hopfner F, Koeglsperger T, Respondek G, Schweyer K, Levin J. Four-repeat
tauopathies. Progress in neurobiology. 2019 Sep 1;180:101644.
8. Summary
Aberrant neuronal and glial tau aggregation.
The regional, morphologic, and cell-type variability with the
resultant vast heterogeneity in clinical illnesses,
underscores the importance of distinct disease-specific
pathomechanisms in tauopathies.
Understanding the mechanisms of tau aggregation and
their role in neurotoxicity based on type of tau aggregate
and cell-type predilection is important.
Various therapeutic strategies are being developed to
target tau from anti-aggregation agents to immunotherapy.
Given the heterogeneity of the disorders, it is unlikely that
an effective therapeutic approach for one type of
tauopathy, or even one subtype, or even in one individual,
may be beneficial for another.
