Astrocyte-neuron communication through the complement C3-C3aR pathway in Parkinson’s disease

Chi, Xiaosa; Yin, Sijia; Sun, Yadi; Kou, Liang; Zou, Wenkai; Wang, Yiming; Jin, Zongjie; Wang, Tao; Xia, Yun

doi:10.1016/j.bbi.2024.09.022

Cited by 2 publications

References 69 publications

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Network analysis of α-synuclein pathology progression reveals p21-activated kinases as regulators of vulnerability

Vatsa,

Brynildsen,

Goralski

et al. 2024

Preprint

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α-Synuclein misfolding and progressive accumulation drives a pathogenic process in Parkinson's disease. To understand cellular and network vulnerability to α-synuclein pathology, we developed a framework to quantify network-level vulnerability and identify new therapeutic targets at the cellular level. Full brain α-synuclein pathology was mapped in mice over 9 months. Empirical pathology data was compared to theoretical pathology estimates from a diffusion model of pathology progression along anatomical connections. Unexplained variance in the model enabled us to derive regional vulnerability that we compared to regional gene expression. We identified gene expression patterns that relate to regional vulnerability, including 12 kinases that were enriched in vulnerable regions. Among these, an inhibitor of group II PAKs demonstrated protection from neuron death and α-synuclein pathology, even after delayed compound treatment. This study provides a framework for the derivation of cellular vulnerability from network-based studies and identifies a promising therapeutic pathway for Parkinson's disease.

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Network analysis of α-synuclein pathology progression reveals p21-activated kinases as regulators of vulnerability

Vatsa,

Brynildsen,

Goralski

et al. 2024

Preprint

View full text Add to dashboard Cite

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Plant derived bioactive compounds for the treatment of neurodegeneration and neuroimmune disorders associated with the complement system

Narayanaperumal,

Gopal

2024

Explor Immunol

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The complement system is a key component of the innate immune system that mediates the clearance of pathogens, apoptotic cells, and cellular debris. However, the complement system also has diverse roles in the central nervous system (CNS), where it regulates synaptic pruning, neural plasticity, and neuroinflammation. Dysregulation of the complement system has been implicated in various neurodegenerative disorders such as Alzheimer’s disease, multiple sclerosis, epilepsy, stroke, and traumatic brain injury. In these conditions, excessive or chronic activation of the complement system may lead to synaptic loss, neuronal damage, immune dysregulation, and inflammation, which leads to exacerbating the disease’s progression and severity. Moreover, the complement system may interact with infectious agents that invade the CNS, such as bacteria, viruses, fungi, and parasites, and modulate their pathogenicity and host response. Therefore, understanding the complex interplay between the complement system and the CNS is crucial for developing novel therapeutic strategies to prevent or treat neurodegenerative and neuroimmune disorders. Natural compounds, such as plant extracts, phytochemicals, and nutraceuticals, have emerged as promising candidates for modulating the complement system and its effects on the CNS. These compounds may exert anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory effects by regulating the expression of various complement components and pathways. In this review, we summarized the current knowledge on the roles of the complement system in human neurodegenerative disorders and the benefits of natural compounds for complement-targeted therapy.

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Astrocyte-neuron communication through the complement C3-C3aR pathway in Parkinson’s disease

Cited by 2 publications

References 69 publications

Network analysis of α-synuclein pathology progression reveals p21-activated kinases as regulators of vulnerability

Network analysis of α-synuclein pathology progression reveals p21-activated kinases as regulators of vulnerability

Plant derived bioactive compounds for the treatment of neurodegeneration and neuroimmune disorders associated with the complement system

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