Tankyrase (TNKS) is a poly-ADP-ribose polymerase (PARP) family member that plays crucial roles in telomere maintenance, Wnt/β-catenin signaling, and protein stability. Tankyrase dysfunction has been implicated in Alzheimer's disease, Parkinson's disease, and various cancers.
Tankyrase (TNKS) is a poly-ADP-ribose polymerase (PARP) family member that plays crucial roles in telomere maintenance, Wnt/β-catenin signaling, and protein stability. Tankyrase dysfunction has been implicated in Alzheimer's disease, Parkinson's disease, and various cancers.
Overview
Tankyrase (TNKS) is a 142 kDa protein encoded by the TNKS gene on chromosome 8p23.1 [@smith2018]. It belongs to the PARP family of enzymes that catalyze ADP-ribosylation of target proteins [@am2019]. A closely related paralog, TNKS2, shares similar functions.
The protein functions as both a scaffold and an enzyme, recruiting diverse substrates and modifying them with poly-ADP-ribose (PAR) chains [@riffell2012].
Normal Function
In the healthy nervous system, tankyrase participates in:
Telomere Maintenance: Regulates telomere length and structure
Wnt/β-catenin Signaling: Controls β-catenin degradation and transcription
Protein Quality Control: Targets proteins for degradation via PARylation
DNA Repair: Facilitates repair of DNA damage
Axonal Development: Regulates axon outgrowth and neuronal polarity
Role in Disease
Alzheimer's Disease (AD)
Tankyrase contributes to AD pathogenesis through multiple mechanisms:
APP Processing: Regulates [amyloid precursor protein](/entities/app-protein) trafficking and processing
[Tau](/proteins/tau) Pathology: Affects tau stability and aggregation
Synaptic Dysfunction: Impairs synaptic plasticity via Wnt pathway
Neuronal Death: PAR accumulation promotes neurotoxicity [@zhang2020]
Parkinson's Disease (PD)
In PD, tankyrase involvement includes:
[α-Synuclein](/proteins/alpha-synuclein) Aggregation: Modulates α-synuclein clearance and aggregation
Mitochondrial Quality Control: Affects mitophagy and mitochondrial dynamics
LRRK2 Regulation: Interacts with LRRK2 kinase activity