# CD4+T cell metabolic reprogramming as therapeutic targets in neurodegenerative diseases

## TL;DR

This paper reviews how CD4+T cell metabolism can be targeted to treat neurodegenerative diseases like Alzheimer's and Parkinson's.

## Contribution

The paper highlights novel therapeutic strategies by focusing on CD4+T cell metabolic reprogramming in neurodegenerative diseases.

## Key findings

- CD4+T cells influence neuroinflammation through distinct metabolic profiles.
- Promoting oxidative phosphorylation and fatty acid oxidation in CD4+T cells may restore regulatory functions.
- Metabolic interventions targeting CD4+T cells could reshape treatment for neurodegenerative disorders.

## Abstract

Neurodegenerative diseases are a group of disorders characterized by the progressive loss of structure and function of neurons in the brain and/or peripheral nervous system. The main pathological feature of neurodegenerative disease in the central nervous system (CNS) is the selective neuronal loss in the brain and spinal cord, leading to cognitive and/or motor dysfunction. The immune system plays a variety of roles in the pathophysiology of neurodegenerative diseases. CD4+T cells are being recognized as important immunometabolic modulators in the pathophysiology of neurodegenerative disorders (ND), including multiple sclerosis (MS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Their varied metabolic patterns provide a special therapeutic window for regulating neuroinflammation, spanning from lipid-dependent regulatory T cells (Tregs) to glycolysis-driven pro-inflammatory subsets (Th1, Th17). Abnormal immune metabolism raises the risk of oxidative stress, mitochondrial malfunction, and neuronal death in neurodegenerative environments. According to recent research, altering CD4 T cell metabolism to favour oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) may help Treg function return and inhibit harmful effector responses. Current research on CD4 T cell immunometabolic pathways, their interactions with CNS-resident cells, and the developing possibility of metabolic intervention to slow neurodegeneration is explained in this review. By examining important signaling pathways including AMPK, mTORC1, and ROS dynamics, we demonstrate how CD4+T cell metabolism may reshape ND treatment approaches.