Neuroinflamazioa Parkinson gaixotasunaren agerpenean eta progresioan

Abstract

Parkinson’s disease (PD) is the most common motor neurodegenerative disorder and to this day, no curative treatment is available. Patients manifest motor symptoms such as resting tremors, muscular rigidity, bradykinesia and postural instability. PD is characterised by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta, causing nigrostriatal pathway dysfunction. Cellular and molecular mechanisms involved in this neuronal death have been described, but the disease pathogenesis is still not fully understood. The main neuropathological characteristic of PD is the presence of Lewy bodies in the brain, mostly composed of α-synuclein protein. For many years, glial cells were considered as mere neuronal support, but recent evidence has revealed their essential roles in brain structure and function. Activated microglia and astrocytes are classified into M1 and A1 proinflammatory and M2 and A2 anti-inflammatory phenotypes. Although exact mechanisms between neuroinflammation and neurodegeneration are unknown, neuroinflammation has been suggested to play a key role. Human studies showed that neuroinflammation is closely related to the onset and progression of PD. Postmortem studies in brains of PD patients have demonstrated glial cell activation, and animal models presented signs of neuroinflammation. Animal models generated by injecting preformed α-synuclein fibrils into the brain best reproduced the pathological findings of PD. Current evidence indicates that neuroinflammation may be an early event in PD pathogenesis, with a peripheral origin. Evidence of peripheral inflammation in PD could lead to α-synuclein accumulation and neuronal degeneration. Early intervention against inflammation may be a useful strategy to prevent or delay PD.