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Astrocyte‐microglia crosstalk is vital for neuronal survival and clearing aggregate accumulation in neurodegenerative diseases. While interleukin‐3 (IL‐3) has been reported to exert both protective and detrimental effects in neurodegenerative diseases, however, its role in α‐synuclein pathology remains unclear. In this study, it is found that astrocytic IL‐3 and microglial IL‐3R are positively responsive to α‐synuclein pathology in the brains of transgenic A53T Parkinson's disease (PD) mice and in an adeno‐associated virus (AAV)‐human α‐synuclein (AAV‐hα‐Syn)‐injected PD mouse model. Exogenous IL‐3 infusion reduces behavioral abnormities and nigrostriatal α‐synuclein pathology. Mechanistically, IL‐3 induces microglial phagocytosis of pathological α‐synuclein while simultaneously stimulating dopaminergic (DA) neurons to clear pathological α‐synuclein via induction of autophagy through the IFN‐β/Irgm1 pathway. Due to its limited efficiency in crossing the blood–brain barrier, a precise IL‐3 delivery strategy is developed by cross‐linking IL‐3 and RVG29 with PEG‐Linker (RVG‐modified IL‐3 nanogels—RVG‐IL3 NGs). Intravenous administration of RVG‐IL3 NGs shows efficient uptake by microglia and DA neurons within the brain. RVG‐IL3 NGs ameliorate motor deficits and pathological α‐synuclein by improving microglial and neuronal function in the AAV‐hα‐Syn mouse model of PD. Collectively, IL‐3 may represent a feasible therapeutic strategy for PD. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease of colon and rectum with unknown etiology, and the lesions are mainly confined to the mucosa and submucosa of large intestine. The main clinical features of UC include diarrhea, abdominal pain, bloody purulent stool and tenesmus, which seriously affect patients' quality of life. Most of UC patients would receive drug therapy with the exception of surgery for some severe cases. However, current drugs for the treatment of UC have certain limitations including difficulty of radical treatment, adverse reactions and drug resistance after long-term use and exorbitant price of some drugs. The research and development of new drugs for the treatment of UC is urgent, and natural alkaloids are an important source. This research paid close attention to the progress of natural alkaloids from diverse medicinal plants for treating UC in the last twenty years. The potential mechanisms for the natural alkaloids in the treatment of UC was closely related to its modulation of oxidative stress, immune response, intestinal flora and improvement of the gut barrier function. Remarkable effectiveness and safety of natural-derived alkaloids make them potential candidates of UC therapy. [Display omitted] [ABSTRACT FROM AUTHOR]