Curcumin protects axons from degeneration in the setting of local neuroinflammation.
نویسندگان
چکیده
Axon degeneration is a hallmark of several central nervous system (CNS) disorders, including multiple sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Previous neuroprotective approaches have mainly focused on reversal or prevention of neuronal cell body degeneration or death. However, experimental evidence suggests that mechanisms of axon degeneration may differ from cell death mechanisms, and that therapeutic agents that protect cell bodies may not protect axons. Moreover, axon degeneration underlies neurologic disability and may, in some cases, represent an important initial step that leads to neuronal death. Here, we develop a novel quantitative microfluidic-based methodology to assess mechanisms of axon degeneration caused by local neuroinflammation. We find that LPS-stimulated microglia release soluble factors that, when applied locally to axons, result in axon degeneration. This local axon degeneration is mediated by microglial MyD88/p38 MAPK signaling and concomitant production of nitric oxide (NO). Intra-axonal mechanisms of degeneration involve JNK phosphorylation. Curcumin, a compound with both anti-oxidant and JNK inhibitory properties, specifically protects axons, but not neuronal cell bodies, from NO-mediated degeneration. Overall, our platform provides mechanistic insights into local axon degeneration, identifies curcumin as a novel axon protectant in the setting of neuroinflammation, and allows for ready screening of axon protective drugs.
منابع مشابه
Ellagic Acid Protects the Brain Against 6-Hydroxydopamine Induced Neuroinflammation in a Rat Model of Parkinson’s Disease
Introduction: Neuroinflammation may play as an important risk factor in progressive degeneration of dopaminergic cells. Antioxidants have protective effects against free radicalsinduced neural damage in Parkinson’s disease (PD). In the present study, we examined the effects of ellagic acid (EA) on locomotion and neuroinflammatory biomarkers in a rat model of PD induced by 6-hydroxidopamin...
متن کاملPhenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo.
Axonal degeneration within the spinal cord contributes substantially to neurological disability in multiple sclerosis (MS). Thus neuroprotective therapies that preserve axons, so that they maintain their integrity and continue to function, might be expected to result in improved neurological outcome. Sodium channels are known to provide a route for sodium influx that can drive calcium influx, v...
متن کاملConsumption of antioxidant dietary agents, curcumin and vitamin C, protects cellular DNA from gamma-radiation
Background: Exposure to ionizing radiation results in genotoxicity and the unrepaired lesions in cellular DNA results in cell cycle arrest, reproductive death, interphase death, division delay, chromosome aberrations, mutations, etc. leading to the intensive destruction of cells and violation of their proliferative capacity there by adversely affecting the mammalian system. Since ionizing radia...
متن کاملCaspase inhibition in neuroinflammation induced by soluble β amyloid monomer, protects cells from abnormal survival and proliferation, via attenuation of NFқB activity
Introduction: Evidence suggests that neuronal apoptosis in neurodegenerative diseases is correlated with inflammatory reactions. The beneficial or detrimental role of apoptosis in neuroinflammation is unclear. Elucidating this question may be helpful in management of neurodegenerative diseases. Since TNF-α is able to induce apoptosis as well as increased viability of the cells by activation ...
متن کاملA local mechanism mediates NAD-dependent protection of axon degeneration
Axon degeneration occurs frequently in neurodegenerative diseases and peripheral neuropathies. Important insight into the mechanisms of axon degeneration arose from findings that the degeneration of transected axons is delayed in Wallerian degeneration slow (Wlds) mice with the overexpression of a fusion protein with the nicotinamide adenine dinucleotide (NAD) synthetic enzyme, nicotinamide mon...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Experimental neurology
دوره 253 شماره
صفحات -
تاریخ انتشار 2014