Peripheral Inflammatory Markers TNF-α and CCL2 Revisited: Association with Parkinson’s Disease Severity

Abstract

One of the major mediators of neuroinflammation in PD is tumour necrosis factor alpha (TNF-α), which, similar to other cytokines, is produced by activated microglia and astrocytes. Although TNF-α can be neuroprotective in the brain, long-term neuroinflammation and TNF release can be harmful, having a neurotoxic role that leads to death of oligodendrocytes, astrocytes, and neurons and, therefore, is associated with neurodegeneration. Apart from cytokines, a wide family of molecules with homologous structures, namely chemokines, play a key role in neuro-inflammation by drawing cytotoxic T-lymphocytes and activating microglia. The objective of the current study was to examine the levels of the serum TNF-α and CCL2 (Chemokine (C-C motif) ligand 2), also known as MCP-1 (Monocyte Chemoattractant Protein-1), in PD patients compared with healthy controls. We also investigated the associations between the serum levels of these two inflammatory mediators and a number of clinical symptoms, in particular, disease severity and cognition. Such an assessment may point to their prognostic value and provide some treatment hints. PD patients with advanced stage on the Hoehn–Yahr scale showed an increase in TNF-α levels compared with PD patients with stages 1 and 2 (p = 0.01). Additionally, the UPDRS score was significantly associated with TNF-α levels. CCL2 levels, however, showed no significant associations.

Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 (MCP-1) and 28-Day Mortality in Elderly Patients with Sepsis: A Retrospective Single-Center Study

“…Additionally, extracellular MCP-1 elicits a pro-inflammatory response, initiating the inflammatory cascade [ 21 , 22 ]. MCP-1 plays a significant role in the development and occurrence of various diseases, including tumors [ 21 ], bone remodeling and metastasis [ 23 ], autoimmune disease [ 24 ], and nervous system disease [ 25 ]. Furthermore, MCP-1 is involved in the local inflammatory response in diverse organs and tissues, including acute kidney injury [ 26 ], acute lung injury [ 27 ], liver inflammation [ 28 ] and liver failure [ 29 ], insulin resistance [ 30 ], neuro-inflammation [ 31 ], cardiac injury [ 32 ], and myocardial ischemic injury [ 33 ].…”

“…The acute kidney injury caused by sepsis was alleviated through TLR2/NF-κB/CCL2 signaling pathway [ 20 ]. MCP-1 has the potential to serve as an indicator of pro-inflammatory phenotypes within the human body [ 15 , 25 ]. It has significant involvement in the inflammatory response to tissue damage and its utility as a biomarker for organ infection injury.…”

Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression

“…Lastly, the role of microglia and inflammation is increasingly recognized in Parkinson’s disease, where dopaminergic neuron loss occurs. Altering Ccl2 activity might impact microglial responses and, consequently, neuronal survival in this context ( 38 ). However, each of these diseases has a distinct pathological process, and the effect of Ccl2 modulation could vary accordingly.…”

Treatment of Parkinson’s disease with biologics that penetrate the blood–brain barrier via receptor-mediated transport

“…TNFα knockout mice have an 8-fold reduction in mortality associated with MPTP administration ( Ferger et al, 2004 ). TNFα is secreted in brain by microglial cells, which plays a pro-inflammatory role in the development of human PD ( Hamid et al, 2022 ; Xiromerisiou et al, 2022 ; Cabrera Ranaldi et al, 2023 ; Wang et al, 2023 ). Microglial production of TNFα in PD results in increased secretion of α-synuclein ( Bae et al, 2022 ).…”