HCH6-1, an antagonist of formyl peptide receptor-1, exerts anti-neuroinflammatory and neuroprotective effects in cellular and animal models of Parkinson’s disease

Wang, Hung‐Li; Cheng, Yi-Chuan; Yeh, Tu-Hsueh; Liu, Han-Fang; Weng, Yi-Hsin; Chen, Rou‐Shayn; Chen, Yi‐Chun; Lu, Jiaqi; Hwang, Tsong‐Long; Wei, Kuo‐Chen; Liu, Yuchuan; Wang, Yuting; Hsu, Chia‐Chen; Chiu, Tai-Ju; Chiu, Ching-Chi

doi:10.1016/j.bcp.2023.115524

Cited by 7 publications

(1 citation statement)

References 56 publications

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“…TNFα knockout mice have an 8-fold reduction in mortality associated with MPTP administration ( Ferger et al, 2004 ). TNFα is secreted in brain by microglial cells, which plays a pro-inflammatory role in the development of human PD ( Hamid et al, 2022 ; Xiromerisiou et al, 2022 ; Cabrera Ranaldi et al, 2023 ; Wang et al, 2023 ). Microglial production of TNFα in PD results in increased secretion of α-synuclein ( Bae et al, 2022 ).…”

Section: Blood–brain Barrier Receptor-mediated Transport Of Igg-decoy...mentioning

confidence: 99%

Treatment of Parkinson’s disease with biologics that penetrate the blood–brain barrier via receptor-mediated transport

Pardridge

2023

Front. Aging Neurosci.

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Parkinson’s disease (PD) is characterized by neurodegeneration of nigral-striatal neurons in parallel with the formation of intra-neuronal α-synuclein aggregates, and these processes are exacerbated by neuro-inflammation. All 3 components of PD pathology are potentially treatable with biologics. Neurotrophins, such as glial derived neurotrophic factor or erythropoietin, can promote neural repair. Therapeutic antibodies can lead to disaggregation of α-synuclein neuronal inclusions. Decoy receptors can block the activity of pro-inflammatory cytokines in brain. However, these biologic drugs do not cross the blood–brain barrier (BBB). Biologics can be made transportable through the BBB following the re-engineering of the biologic as an IgG fusion protein, where the IgG domain targets an endogenous receptor-mediated transcytosis (RMT) system within the BBB, such as the insulin receptor or transferrin receptor. The receptor-specific antibody domain of the fusion protein acts as a molecular Trojan horse to ferry the biologic into brain via the BBB RMT pathway. This review describes the re-engineering of all 3 classes of biologics (neurotrophins, decoy receptor, therapeutic antibodies) for BBB delivery and treatment of PD. Targeting the RMT pathway at the BBB also enables non-viral gene therapy of PD using lipid nanoparticles (LNP) encapsulated with plasmid DNA encoding therapeutic genes. The surface of the lipid nanoparticle is conjugated with a receptor-specific IgG that triggers RMT of the LNP across the BBB in vivo.

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Section: Blood–brain Barrier Receptor-mediated Transport Of Igg-decoy...mentioning

confidence: 99%

Treatment of Parkinson’s disease with biologics that penetrate the blood–brain barrier via receptor-mediated transport

Pardridge

2023

Front. Aging Neurosci.

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Gene Regulation of Neutrophils Mediated Liver and Lung Injury through NETosis in Acute Pancreatitis

Liu,

Zheng,

Meng

et al. 2024

Inflammation

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The role of ZC3H12D-regulated TLR4-NF-κB pathway in LPS-induced pro-inflammatory microglial activation

Long,

Li,

Yao

et al. 2024

Neuroscience Letters

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HCH6-1, an antagonist of formyl peptide receptor-1, exerts anti-neuroinflammatory and neuroprotective effects in cellular and animal models of Parkinson’s disease

Cited by 7 publications

References 56 publications

Treatment of Parkinson’s disease with biologics that penetrate the blood–brain barrier via receptor-mediated transport

Treatment of Parkinson’s disease with biologics that penetrate the blood–brain barrier via receptor-mediated transport

Gene Regulation of Neutrophils Mediated Liver and Lung Injury through NETosis in Acute Pancreatitis

The role of ZC3H12D-regulated TLR4-NF-κB pathway in LPS-induced pro-inflammatory microglial activation

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