Targeting metabolic inflammation in Parkinson’s disease: Implications for prospective therapeutic strategies

Abstract

1. Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the aetiology of PD has not been clarified as yet, it is believed that ageing, diet, diabetes and adiposity are associated with PD. 2. Type 2 diabetes and lipid abnormalities share multiple common pathophysiological mechanisms with PD. In particular, inflammation plays a critical role in the destruction of both pancreatic islet β-cells and dopaminergic neurons in the substantia nigra. Emerging evidence indicates that dysfunctions of energy metabolism evoke metabolic inflammation, which differs to the narrow concept of inflammation, participating in systemic pathological processes such as neurodegenerative disease and diabetes. 3. The brain is considered an immunologically privileged organ, free from immune reactions, because it is protected by the blood-brain barrier (BBB). However, studies have shown that there is gradual impairment of neurovascular function with ageing and in neurodegenerative disorders, resulting in abnormal states, including increased BBB permeability. Consequently, harmful elements that would not normally be able to cross the BBB, such as pro-inflammatory factors, reactive oxygen species and neurotoxins, infiltrate into the brain, triggering neural injury. 4. Currently, the drugs available for the treatment of PD only ameliorate the symptoms of the disease. Therapeutic strategies aimed at stopping or modifying disease progression are still being sought. Most recent studies suggest that both central and peripheral inflammation may be dysregulated in PD. Therefore, therapeutic strategies aimed at modulating systemic inflammatory reactions or energy metabolism may represent a goal in neuroprotection in PD.

Angiotensin II AT1 receptor blockers as treatments for inflammatory brain disorders

“…Parkinson’s disease is an age-associated degenerative condition where inflammation also plays a significant role [235,236]. …”

Systems-Level G Protein-Coupled Receptor Therapy Across a Neurodegenerative Continuum by the GLP-1 Receptor System

“…PD-associated LRRK2 mutations may sensitize microglia cells toward a pro-inflammatory state, which in turn results in exacerbated inflammation with consequent neurodegeneration (112). Inflammatory pathways in PD appear to play a crucial role in the destruction of both pancreatic islet β-cells and dopaminergic neurons in the substantia nigra (113). Emerging evidence indicates that system-wide metabolic dysfunction in PD can induce metabolic inflammation, thus exacerbating the neurodegenerative activity in this disorder.…”

Провокуючі Фактори Дебюту Моторних Симптомів Хвороби Паркінсона

“…Несмотря на многочисленные научные иссле-дования, этиологическая причина заболевания остается неизвестной. К настоящему времени доказано влияние нескольких факторов, которые ведут к потере нейронов ЧС: токсины окружающей среды (пестициды, герби-циды и другие ядохимикаты), митохондриальная дис-функция, оксидативный стресс, воздействие свободных радикалов, генетические факторы, нейровоспаление (воздействие инфекционного агента или токсическо-го вещества с провоспалительными свойствами) [1][2][3]. Данные факторы приводят к развитию БП как инди-видуально, так и при совместном воздействии.…”