REVIEW article

Front. Cell. Neurosci.

Sec. Cellular Neurophysiology

Volume 19 - 2025 | doi: 10.3389/fncel.2025.1627305

Neuromodulation influences T lymphocyte calcium signalling and alpha synuclein clearance: Implications for Parkinson's Disease

Provisionally accepted
Alysia  RossAlysia Ross1Natalie  ProwseNatalie Prowse1Hui  ZhangHui Zhang2Shawn  HayleyShawn Hayley1*Hongyu  SunHongyu Sun1*
  • 1Department of Neuroscience, Carleton University, Ottawa, PA, Canada
  • 2Queensway Carleton Hospital, Nepean, Canada

The final, formatted version of the article will be published soon.

Along with the death of midbrain dopamine neurons, pathological accumulation of aggregated alpha synuclein (a-syn), often in the form of Lewy bodies, forms the hallmark pathological features of Parkinson's Disease (PD). Evidence of a neuroinflammatory response is a common secondary feature present in virtually all PD brains and is characterized by the presence of reactive microglial cells and signs of peripheral immune cell infiltration. Recent research has even suggested that PD might actually have an autoimmune component, as some PD patients express T cells that recognize epitopes specific to a-syn. Although neuromodulation is one of the leading treatment options for PD motor symptoms through regulating neuronal excitability, its impact on underlying a-syn and neuroimmune pathology remains poorly understood. While immune cells, such as T lymphocytes, have historically been thought to be non-excitable cells, their expression of L-type Ca 2+ channels may suggest otherwise. In fact, these channels are thought to have an important role in CD4+ and CD8+ T cell proliferation, survival and cytokine release. Since emerging evidence suggests a-syn-specific T cell responses may be important in PD, we posit that neuromodulatory treatments may be useful for "reprogramming" T cell functioning. In this review, we will summarize the role of a-syn specific T cell responses in PD pathology and consider the role of L-type Ca 2+ channels on CD4+ and CD8+ T cells responses in the disease. We will then discuss the effect of neuromodulatory treatments on T cell-mediated immune responses and a-syn structure in an attempt to explain why treatments involving electrical stimulation are beneficial for PD patients.

Keywords: Parkinson's disease, Neuromodulation, T cell, alpha-Synuclein, voltage-gated calcium channels

Received: 12 May 2025; Accepted: 30 Jun 2025.

Copyright: © 2025 Ross, Prowse, Zhang, Hayley and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Shawn Hayley, Department of Neuroscience, Carleton University, Ottawa, 19104, PA, Canada
Hongyu Sun, Department of Neuroscience, Carleton University, Ottawa, 19104, PA, Canada

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.