Neuroinflammation and noradrenergic modulation with β2-adrenoceptors: Emerging therapeutic targets for Parkinson’s diseases

Abstract Neurodegenerative disorders, such as Parkinson’s disease, are strongly influenced by neuroinflammatory processes and dysfunction of the locus coeruleus-noradrenergic system. The locus coeruleus-noradrenergic system plays a pivotal role in modulating neuroinflammation and maintaining homeostatic regulation in the central nervous system. This review discusses the structural and functional aspects of the locus coeruleus-noradrenergic system and its interaction with immune responses. We examine how neuroinflammation contributes to disease progression, with a focus on glial activation and peripheral-central immune communication. Additionally, we analyze the impact of β-adrenoceptor-targeting drugs, highlighting the contrasting roles of β-blockers and β2-adrenoceptor agonists in neurodegeneration. While β-blocker, particularly non-selective agents like propranolol, have been associated with exacerbated neuroinflammation and Parkinson’s disease risk, β2-adrenoceptor agonists demonstrate neuroprotective effects by modulating microglial phenotypes, reducing α-synuclein aggregation, and enhancing neurotrophic support. Finally, we explore the canonical and non-canonical β2-adrenoceptor signaling pathways implicated in neuroprotection. Collectively, this review supports β2-adrenoceptors as promising therapeutic targets and underscores the need for further studies to elucidate their mechanistic roles in modulating neurodegenerative processes.