Role of Pentoxifylline and Celecoxib in Parkinsonism

Summary

Parkinson's disease (PD) is a chronic neurodegenerative disease clinically characterized by bradykinesia, hypokinesia, rigidity, resting tremor, and postural instability. These motor manifestations are attributed to the degeneration and selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), leading to a dopamine (DA) deficiency in the striatum. The environmental factors are the most common risk factor for Parkinson's disease, while hereditary determinants have minor role for disease. Furthermore, the clinical diagnosis of PD rests on the identification of characteristics related to dopamine deficiency. However, nondopaminergic and nonmotor symptoms, including cognitive dysfunction and depression, which is one of the most common and persistent symptoms, are sometimes present at an earlier disease stage and, almost inevitably, emerge with the disease progression. Neuroinflammation is considered one of the most important factors contributing critically to pathophysiology of PD . Recently, high mobility group box-1 (HMGB1) protein has been encoded as a potential inflammatory biomarker in PD. HMGB1 mediates immune response mostly through endothelial cells and macrophage activation via targeting two vital cell receptors; Toll-like receptor 4 (TLR4) and advanced glycation end products (RAGE). HMGB1 leads to a sequential cascade of inflammatory response through enhanced release of tumor necrosis factor-alpha (TNF-α) and interleukins (ILs), prominently IL-1β and IL-6. HMGB1 mediated also up-regulation of nuclear factor kappa-β (NF-κB) with subsequent flared pro-inflammatory storm.

Timeline

Start

2023-08-07

Primary completion

2024-09-20

Completion

2024-09-20

Publications

• Khrieba MO, Hegazy SK, Mohammed WF, El-Haggar SM. Clinical study to investigate the adjuvant role of Pentoxifylline in patients with Parkinson's disease: A randomized controlled study. Int Immunopharmacol. 2025 May 27;156:114689. doi: 10.1016/j.intimp.2025.114689. Epub 2025 Apr 19.
• Khrieba MO, Hegazy SK, Mustafa W, El-Haggar SM. Repurposing celecoxib as adjuvant therapy in patients with Parkinsonian disease: a new therapeutic dawn: randomized controlled pilot study. Inflammopharmacology. 2024 Dec;32(6):3729-3738. doi: 10.1007/s10787-024-01567-z. Epub 2024 Sep 28.

Drugs

Indications