Research Projects

Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), leading to classical motor symptoms such as bradykinesia, rigidity, and postural instability (Dauer and Przedborski, 2003; Moustafa et al., 2016). In recent years, PD has increasingly been recognized as a multisystem disorder that includes a wide range of non-motor symptoms such as neuroinflammation, autonomic dysfunction, cognitive decline, and fatigue (Tansey et al., 2007; Radad et al., 2023). Among these, central inflammation and sympathetic nervous system (SNS) dysfunction are emerging as critical contributors to disease progression and systemic complications (Sabino-Carvalho et al., 2021; Tansey et al., 2007). Skeletal muscle function and regeneration are controlled by a complex interplay between local factors—such as muscle stem cells (MuSCs) and peripheral motor innervation—as well as central mechanisms (Mukund and Subramaniam, 2020; Matthews et al., 2023). Among central regulators, SNS is vital in modulating muscle blood flow, metabolism, and regeneration (Benarroch, 2024), while neuroinflammation—marked by activation of microglia and elevated proinflammatory cytokine levels such as TNF-α, IL-1β, and IL-6—is a central feature of PD pathophysiology (Isik et al., 2023). Neuroinflammatory signals can extend their influence beyond the central nervous system (CNS), altering systemic homeostasis and affecting peripheral tissues (Ferrari and Tarelli, 2011; Dong-Chen et al., 2023). Despite evidence supporting the individual contributions of neuroinflammation and sympathetic dysfunction in PD, the integrated impact of these central disturbances due to PD on skeletal muscle homeostasis and regenerative potential remains unexplored. This study hypothesizes that PD-induced neuroinflammatory signaling and impaired sympathetic outflow collectively disrupt skeletal muscle homeostasis by altering the activation and differentiation of MuSCs, reducing regenerative capacity, and promoting progressive muscle atrophy. Using a well-established 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian mouse model, this study aims to dissect the temporal effects of neuroinflammation and SNS dysfunction on skeletal muscle structure, function, and MuSC behavior. Furthermore, the study will evaluate the therapeutic potential of two pharmacological interventions: minocycline, an anti-inflammatory agent known to suppress microglial activation, and propranolol, a β-adrenergic blocker that modulates sympathetic activity. Their individual and combined efficacy in preserving muscle integrity will be assessed through histological, molecular, and cellular analyses. These findings are likely to offer valuable insights not only into PD pathophysiology but also into broader applications involving neurodegeneration-induced systemic deterioration.