Tau protein: Difference between revisions

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'''Tau protein''' is a protein that in humans is encoded by the MAPT gene. It is abundant in the nervous system and is involved in the stabilization of microtubules in the axons of neurons. Tau proteins interact with tubulin to stabilize microtubules and promote tubulin assembly into microtubules. Tau has two ways of controlling microtubule stability: isoforms and phosphorylation.
{{Short description|A protein associated with microtubule stabilization and neurodegenerative diseases}}


==Structure==
'''Tau protein''' is a [[protein]] that plays a critical role in the stabilization of [[microtubules]] in [[neurons]]. It is predominantly found in the [[central nervous system]] and is associated with several [[neurodegenerative diseases]], collectively known as [[tauopathies]].
Tau proteins are produced through alternative splicing of a single gene that in humans is designated MAPT (microtubule-associated protein tau). Six tau isoforms exist in brain tissue. These isoforms differ from each other by the presence or absence of one to four repeat domains in the carboxy-terminal half of the molecule. The repeat domains, which are located towards the carboxy terminus of the protein, bind to microtubules and are responsible for the protein's microtubule-binding activity.


==Function==
==Structure and Function==
Tau proteins are involved in microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The tau proteins, especially in neuronal cells, constantly interact with tubulin to stabilize microtubules and promote tubulin assembly into microtubules. Tau is absent from the cell body and is present in axons.
Tau protein is a member of the [[microtubule-associated proteins]] (MAPs) family. It is primarily expressed in neurons, where it binds to and stabilizes microtubules, which are essential components of the [[cytoskeleton]]. Microtubules are involved in maintaining cell shape, enabling intracellular transport, and facilitating cell division.


==Clinical significance==
Tau protein is encoded by the [[MAPT gene]] located on [[chromosome 17]]. The protein undergoes alternative splicing, resulting in six isoforms in the adult human brain. These isoforms differ in the number of microtubule-binding repeats and the presence of N-terminal inserts, which influence their binding affinity to microtubules.
Abnormalities in tau protein function and its interaction with microtubules have been linked to a variety of neurological disorders, including Alzheimer's disease, Pick's disease, and frontotemporal dementia and parkinsonism linked to chromosome 17. In these diseases, tau proteins become hyperphosphorylated, leading to the formation of neurofibrillary tangles and the disintegration of microtubules in brain cells.


[[Category:Proteins]]
==Role in Neurodegenerative Diseases==
[[Category:Neurology]]
Tau protein is implicated in a group of neurodegenerative disorders known as tauopathies. The most well-known of these is [[Alzheimer's disease]], where abnormal hyperphosphorylation of tau leads to the formation of [[neurofibrillary tangles]] (NFTs). These tangles disrupt neuronal function and are a hallmark of the disease.
[[Category:Alzheimer's disease]]
 
[[Category:Parkinson's disease]]
Other tauopathies include:
* [[Progressive supranuclear palsy]]
* [[Corticobasal degeneration]]
* [[Frontotemporal dementia with parkinsonism linked to chromosome 17]] (FTDP-17)
 
In these conditions, tau protein undergoes pathological changes, including hyperphosphorylation, truncation, and aggregation, leading to neuronal dysfunction and cell death.
 
==Pathophysiology==
The pathophysiological mechanisms of tau-related neurodegeneration involve several processes:
 
* '''Hyperphosphorylation''': Abnormal phosphorylation of tau reduces its affinity for microtubules, causing it to detach and aggregate into insoluble filaments.
* '''Aggregation''': Detached tau proteins aggregate into paired helical filaments (PHFs) and straight filaments, which form the core of neurofibrillary tangles.
* '''Cellular Dysfunction''': The accumulation of tau aggregates disrupts cellular processes, including axonal transport, synaptic function, and neuronal communication.
 
==Research and Therapeutic Approaches==
Research into tau protein focuses on understanding its normal function, the mechanisms of its pathological transformation, and developing therapeutic strategies to prevent or reverse tau-related neurodegeneration.
 
Therapeutic approaches include:
* '''Tau-targeting drugs''': Small molecules or antibodies that inhibit tau aggregation or promote its clearance.
* '''Gene therapy''': Techniques to modulate tau expression or correct mutations in the MAPT gene.
* '''Phosphorylation inhibitors''': Compounds that prevent abnormal phosphorylation of tau.
 
==Images==
[[File:Tau_protein_structure.png|thumb|right|Diagram of tau protein structure showing microtubule-binding domains.]]


{{stub}}
[[File:Neurofibrillary_tangles.png|thumb|left|Histological image of neurofibrillary tangles in Alzheimer's disease.]]


==See also==
==Related pages==
* [[Microtubule]]
* [[Microtubule]]
* [[Neurodegenerative disease]]
* [[Alzheimer's disease]]
* [[Alzheimer's disease]]
* [[Parkinson's disease]]
* [[Frontotemporal dementia]]
* [[Frontotemporal dementia]]
* [[Pick's disease]]


==References==
[[Category:Proteins]]
<references />
[[Category:Neurodegenerative disorders]]
 
[[Category:Tauopathies]]
==External links==
* [https://www.ncbi.nlm.nih.gov/gene/4137 MAPT gene] at NCBI
* [https://www.uniprot.org/uniprot/P10636 Tau protein] at UniProt
 
{{Proteins}}
{{Neurology}}
{{Alzheimer's disease}}
{{Parkinson's disease}}
== Tau protein ==
<gallery>
File:MAP2-tau_in_neurons.jpg
File:tau1.jpg
</gallery>

Revision as of 17:44, 18 February 2025

A protein associated with microtubule stabilization and neurodegenerative diseases


Tau protein is a protein that plays a critical role in the stabilization of microtubules in neurons. It is predominantly found in the central nervous system and is associated with several neurodegenerative diseases, collectively known as tauopathies.

Structure and Function

Tau protein is a member of the microtubule-associated proteins (MAPs) family. It is primarily expressed in neurons, where it binds to and stabilizes microtubules, which are essential components of the cytoskeleton. Microtubules are involved in maintaining cell shape, enabling intracellular transport, and facilitating cell division.

Tau protein is encoded by the MAPT gene located on chromosome 17. The protein undergoes alternative splicing, resulting in six isoforms in the adult human brain. These isoforms differ in the number of microtubule-binding repeats and the presence of N-terminal inserts, which influence their binding affinity to microtubules.

Role in Neurodegenerative Diseases

Tau protein is implicated in a group of neurodegenerative disorders known as tauopathies. The most well-known of these is Alzheimer's disease, where abnormal hyperphosphorylation of tau leads to the formation of neurofibrillary tangles (NFTs). These tangles disrupt neuronal function and are a hallmark of the disease.

Other tauopathies include:

In these conditions, tau protein undergoes pathological changes, including hyperphosphorylation, truncation, and aggregation, leading to neuronal dysfunction and cell death.

Pathophysiology

The pathophysiological mechanisms of tau-related neurodegeneration involve several processes:

  • Hyperphosphorylation: Abnormal phosphorylation of tau reduces its affinity for microtubules, causing it to detach and aggregate into insoluble filaments.
  • Aggregation: Detached tau proteins aggregate into paired helical filaments (PHFs) and straight filaments, which form the core of neurofibrillary tangles.
  • Cellular Dysfunction: The accumulation of tau aggregates disrupts cellular processes, including axonal transport, synaptic function, and neuronal communication.

Research and Therapeutic Approaches

Research into tau protein focuses on understanding its normal function, the mechanisms of its pathological transformation, and developing therapeutic strategies to prevent or reverse tau-related neurodegeneration.

Therapeutic approaches include:

  • Tau-targeting drugs: Small molecules or antibodies that inhibit tau aggregation or promote its clearance.
  • Gene therapy: Techniques to modulate tau expression or correct mutations in the MAPT gene.
  • Phosphorylation inhibitors: Compounds that prevent abnormal phosphorylation of tau.

Images

File:Tau protein structure.png
Diagram of tau protein structure showing microtubule-binding domains.
File:Neurofibrillary tangles.png
Histological image of neurofibrillary tangles in Alzheimer's disease.

Related pages