Expression of G2019S LRRK2 in Rat Primary Astrocytes Mediates Neurotoxicity and Alters the Dopamine Synthesis Pathway in N27 Cells via Astrocytic Proinflammatory Cytokines and Neurotrophic Factors DOI Creative Commons
Dong Hwan Ho, Hye Jung Kim, Daleum Nam

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(5), P. 4324 - 4336

Published: May 6, 2024

Astrocytes in the brain contribute to various essential functions, including maintenance of neuronal framework, survival, communication, metabolic processes, and neurotransmitter levels. Leucine-rich repeat kinase 2 (LRRK2) is associated with pathogenesis Parkinson’s disease (PD). LRRK2 expressed neurons, microglia, astrocytes plays diverse roles these cell types. We aimed determine effects mutant human G2019S-LRRK2 (GS-hLRRK2) rat primary (rASTROs). Transfection GS-hLRRK2 significantly decreased viability compared transfection vector wild-type (WT-hLRRK2). expression reduced levels nerve growth factor increased proinflammatory cytokines (interleukin-1β tumor necrosis α) WT-hLRRK2 expression. Furthermore, rASTROs promoted astrogliosis, which was characterized by glial fibrillary acidic protein vimentin. Treatment conditioned medium G2019S LRRK2-expressing N27 treatment that WT-hLRRK2-expressing rASTROs. Consequently, regulation dopamine synthesis pathway affected cells, thereby leading altered tyrosine hydroxylase, transporter, Nurr1, release. Overall, mutation disrupted astrocyte function, aggravating PD progression.

Language: Английский

New Insight into Neuropathic Pain: The Relationship between α7nAChR, Ferroptosis, and Neuroinflammation DOI Open Access

Fangting Luo,

Cheng Huang

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6716 - 6716

Published: June 18, 2024

Neuropathic pain, which refers to pain caused by a lesion or disease of the somatosensory system, represents wide variety peripheral central disorders. Treating neuropathic is quite demanding, primarily because its intricate underlying etiological mechanisms. The nervous system relies on microglia maintain balance, as they are associated with serving primary immune responses in brain next cell communication. Ferroptosis, driven phospholipid peroxidation and regulated iron, vital mechanism death regulation. Neuroinflammation can be triggered ferroptosis microglia, contributes release inflammatory cytokines. Conversely, neuroinflammation induce iron accumulation resulting microglial ferroptosis. Accumulating evidence suggests that neuroinflammation, characterized glial activation substances, significantly exacerbates development pain. By inhibiting ferroptosis, it may possible prevent subsequently alleviate homopentameric α7 subtype neuronal nicotinic acetylcholine receptor (α7nAChR) has potential suppress activation, transitioning M1 an M2 phenotype, facilitating anti-inflammatory factors, ultimately reducing Recent years have witnessed growing recognition regulatory role α7nAChR could target for treating This review summarizes mechanisms related progress according recent research. Such exploration will help elucidate relationship between α7nAChR, provide new insights into management.

Language: Английский

Citations

5
Targeting cytokine networks in neuroinflammatory diseases DOI
Burkhard Becher, Tobias Derfuß, Roland Liblau

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(11), P. 862 - 879

Published: Sept. 11, 2024

Language: Английский

Citations

5
Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission DOI
Fei Wang, Yu Wang, Qingyang Zhang

et al.

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(7), P. 1381 - 1392

Published: March 21, 2024

Language: Английский

Citations

4
Mouse serum albumin induces neuronal apoptosis and tauopathies DOI Creative Commons

Shengjie Hou,

Yaru Huang, Jie Zhu

et al.

Acta Neuropathologica Communications, Journal Year: 2024, Volume and Issue: 12(1)

Published: April 23, 2024

Abstract The elderly frequently present impaired blood–brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, most abundant protein in plasma, leaking through disrupted BBB, contributes to neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes A1 phenotype remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis endoplasmic reticulum stress response pathway. Moreover, MSA-activated triggered remarkable tau phosphorylation at multiple sites NLRP3 inflammasome Intracerebroventricular injection MSA into brains C57BL/6J mice a similar concentration as patient apoptosis, neuroinflammation, increased phosphorylation, decreased spatial learning memory abilities, while Elovl1 knockdown prevented deleterious effect MSA. Overall, our study revealed neuron apoptosis based on astrocytes, respectively, showing critical roles initiating occurrence tauopathies cognitive decline, providing potential therapeutic targets MSA-induced disorders.

Language: Английский

Citations

4
Expression of G2019S LRRK2 in Rat Primary Astrocytes Mediates Neurotoxicity and Alters the Dopamine Synthesis Pathway in N27 Cells via Astrocytic Proinflammatory Cytokines and Neurotrophic Factors DOI Creative Commons
Dong Hwan Ho, Hye Jung Kim, Daleum Nam

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(5), P. 4324 - 4336

Published: May 6, 2024

Astrocytes in the brain contribute to various essential functions, including maintenance of neuronal framework, survival, communication, metabolic processes, and neurotransmitter levels. Leucine-rich repeat kinase 2 (LRRK2) is associated with pathogenesis Parkinson’s disease (PD). LRRK2 expressed neurons, microglia, astrocytes plays diverse roles these cell types. We aimed determine effects mutant human G2019S-LRRK2 (GS-hLRRK2) rat primary (rASTROs). Transfection GS-hLRRK2 significantly decreased viability compared transfection vector wild-type (WT-hLRRK2). expression reduced levels nerve growth factor increased proinflammatory cytokines (interleukin-1β tumor necrosis α) WT-hLRRK2 expression. Furthermore, rASTROs promoted astrogliosis, which was characterized by glial fibrillary acidic protein vimentin. Treatment conditioned medium G2019S LRRK2-expressing N27 treatment that WT-hLRRK2-expressing rASTROs. Consequently, regulation dopamine synthesis pathway affected cells, thereby leading altered tyrosine hydroxylase, transporter, Nurr1, release. Overall, mutation disrupted astrocyte function, aggravating PD progression.

Language: Английский

Citations

4