# ZCCHC17: a target for synaptic dysfunction and neuronal excitability in Alzheimer’s disease

## TL;DR

This paper explores how the protein ZCCHC17 may regulate synaptic dysfunction and neuronal hyperexcitability in Alzheimer's disease, offering new insights for early diagnosis and treatment.

## Contribution

The paper identifies ZCCHC17 as a potential master regulator of synaptic dysfunction and neuronal excitability in Alzheimer’s disease.

## Key findings

- Reduced ZCCHC17 levels in the Alzheimer’s brain lead to abnormal RNA processing and neuronal hyperexcitability.
- ZCCHC17 appears to play a key role in regulating synaptic dysfunction before gliosis and neuronal loss occur.
- Understanding ZCCHC17's role could improve early diagnostics and therapeutic strategies for Alzheimer’s.

## Abstract

Epileptic activity and neuronal excitability have been reported in the setting of Alzheimer’s disease (AD), and may be linked to disease progression and severity. A shift in the excitation/inhibition balance to favor a more excitatory-dominant outcome appears to underlie the overall hyperactivity, with key mechanisms known to regulate excitatory and inhibitory neurotransmission in the brain being primarily affected. Synaptic dysfunction is a critical event in AD pathogenesis. Recent research suggests that the zinc finger protein, ZCCHC17 (Zinc Finger CCHC-Type Containing 17), serves as a potential master regulator of synaptic dysfunction in AD, with expression significantly reduced in the AD brain prior to gliosis and neuronal loss. Reduced levels of ZCCHC17 have been shown to lead to abnormal RNA processing and neuronal hyperexcitability. This review examines the specific role of ZCCHC17 in the AD brain, and discusses how ZCCHC17 may regulate mechanisms that underlie neuronal hyperexcitability. New insight into synaptic regulators of disease may contribute to improvements in early-stage diagnostics and interventions, and may better guide therapeutic approaches aimed at rescuing synaptic dysfunction in the prodromal stages of AD.