鞘内自体凝血酶激活的浓缩血小板细胞因子在慢性神经退行性疾病中的作用:抗炎和再生反应假说。

Neuro endocrinology letters Pub Date : 2023-09-29
E Scott Sills, Howard I Chu, Jing-Wen Wang, Samuel H Wood, Seang Lin Tan
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引用次数: 0

摘要

脉络丛功能不全或淋巴结淤滞通常被归类为神经退行性疾病中有毒蛋白质有害积累的前传。认知能力下降和神经元信号紊乱随后成为阿尔茨海默病(AD)的主要特征,通常伴随淀粉样蛋白和tau蛋白的积累而进展。对于帕金森病(PD),α-突触核蛋白沉积和多巴胺耗竭与运动受损、静息震颤和强直有关。重要的是,这两种诊断都以高炎症和鞘内细胞因子变化为特征。到目前为止,许多临床试验都没有产生对AD或PD有效的结果,但在这种情况下,自体富血小板血浆(PRP)的抗炎和再生潜力在很大程度上仍未得到检验。我们的报告探讨了一项关于凝血酶激活的PRP鞘内浓缩血浆生长因子作为AD或PD单一疗法的I期研究。这一概念得到了相关工作的支持,其中血小板来源的细胞因子成功降低了炎症,纠正了背景纤维化,失活了异常细胞,并恢复局部组织功能,这些都是AD和PD的理想结果。虽然PRP介导的对膜电位、细胞信号传导、电解质平衡和水分清除的影响尚不清楚,但实验数据表明,这些途径同样可以影响淋巴引流以改善蛋白质病。鞘内PRP及其衍生物作为一种耐受性良好、无超敏风险的“原生物制剂”,比合成药物具有优势。如果AD和PD中与年龄相关的神经炎症是引发或促成神经破坏的上游事件,那么通过患者自身的血小板细胞因子抑制局部氧化应激(在其他情况下成功)也可以为这些神经退行性疾病提供治疗相关性。
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Intrathecal autologous thrombin-activated condensed platelet cytokines in chronic neurodegenerative disease: A hypothesis for anti-inflammatory and regenerative response.

Choroid plexus insufficiency or glymphatic stasis are often classified as prequels to harmful accretion of toxic proteins in neurodegenerative disease. Cognitive decline and disordered neuronal signaling subsequently become cardinal features of Alzheimer's disease (AD), typically progressing with amyloid-ß and tau protein accumulation. For Parkinson's disease (PD), α-synuclein deposits and dopamine depletion are linked to impaired movement, resting tremor, and rigidity. Importantly, both diagnoses feature hyperinflammation and intrathecal cytokine changes. Thus far, numerous clinical trials have produced nothing effective for AD or PD, yet the anti-inflammatory and regenerative potential of autologous platelet-rich plasma (PRP) remains largely unexamined in this context. Our report explores a proposed Phase I study on intrathecal condensed plasma growth factors processed from thrombin-activated PRP as monotherapy for AD or PD. The concept gains support from related work where cytokines of platelet origin successfully lowered inflammation, corrected background fibrosis, deactivated abnormal cells, and recovered local tissue function-all desirable outcomes in AD and PD. While PRP-mediated effects on membrane potentials, cellular signaling, electrolyte balance, and water clearance are less well characterized, experimental data suggest these pathways could likewise influence glymphatic drainage to ameliorate proteinopathies. As a well-tolerated 'orthobiologic' with no hypersensitivity risk, intrathecal PRP and its derivatives bring advantages over synthetic pharmaceuticals. If age-associated neuroinflammation in AD and PD is an upstream event inciting or contributing to neural disruption, then dampening local oxidative stress by a patient's own platelet cytokines (successful in other contexts) could offer therapeutic relevance to these neurodegenerative conditions as well.

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