Lipoic acid might be useful for those with neuropathic pain and maybe as part of a combinatorial strategy for treatment of spinal cord injury.
From 2009:
There is evidence lipoic acid acts similarly to lithium on neurite outgrowth.5. Clinical and therapeutic effects of LA
5.1. Diabetic polyneuropathies
The interaction of LA with regulatory components of the insulin- signaling cascade has proved functionally beneficial to skeletal muscle glucose uptake, whole-body glucose tolerance, and helpful against insulin resistance in animal models [118,120]. Improvements in glucose disposal were also observed in human patients with type 2 diabetes receiving LA either intravenously or orally [120–122]. Several clinical trials have been conducted to measure the efficacy of racemic LA in decreasing symptoms of diabetic polyneuropathies; these are the “alpha-lipoic acid in diabetic neuropathy” (ALADIN) trials and the “symptoms of diabetic polyneuropathy” (SYDNEY) trials. LA was given orally, intravenously, or i.v. with oral follow-up. A meta-analysis of four clinical trials using i.v. LA, including ALADIN, SYDNEY, and the first 3 weeks of ALADIN III, showed a significant improvement in diabetic polyneuropathies of the feet and lower limbs in patients infused with LA 600 mg/day, for three weeks [123]. Diabetic patients in the ALADIN II trial were administered with LA i.v. at 600 or 1200 mg/day for 5 days, then oral LA for 2 years, resulting in improved indices of neuropathy [38]. Patients in the ALADIN III study received LA (600 mg/day i.v.) or placebo for three weeks, followed by oral LA (600 mg t.i.d.) or placebo for 6 months. The oral phase of this trial, however, was without clinically significant benefits [39]. One possible conclusion from these studies was that LA administered intravenously was more efficacious than oral LA, which may be due to either greater bioavailability or poor solubility of the medication in the stomach acid. However, some additional studies have found that oral LA is very effective. For example, the oral pilot (ORPIL) study showed a reduction in diabetic polyneuropathic symptoms after three weeks with 600 mg LA t.i.d. [41]. While the first SYDNEY trial used i.v. LA, [42], the SYDNEY II study used oral LA at 600, 1200, or 1800 mg q.d. for 5 weeks [43]; consequently, both studies showed significant improvements in neuropathic endpoints.
From 2011:
1. Int J Dev Neurosci. 2011 Jun;29(4):415-22. doi: 10.1016/j.ijdevneu.2011.03.001. Epub 2011 Mar 21. MEK/ERKs signaling is essential for lithium-induced neurite outgrowth in N2a cells. Wang Z, Wang J, Li J, Wang X, Yao Y, Zhang X, Li C, Cheng Y, Ding G, Liu L, Ding Z. Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300, Nanjing 210029, China. Lithium, a drug used for the treatment of bipolar disorder, has been shown to affect different aspects of neuronal development such as neuritogenesis, neurogenesis and survival. The underlying mechanism responsible for lithium's influence on neuronal development, however, still remains to be elucidated. In the present study, we demonstrate that lithium increases the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt) and promotes neurite outgrowth in mouse N2a neuroblastoma cells (N2a). The inactivation of mitogen-activated protein kinase kinase (MEK)/ERKs signaling with a MEK inhibitor inhibits neurite outgrowth, but it enhances Akt activation in lithium-treated N2a cells. Furthermore, the inactivation of phosphoinositide-3-kinase (PI3K)/Akt signaling with a PI3K inhibitor increases both lithium-induced ERKs activation and lithium-induced neurite outgrowth. Taken together, our study suggests that lithium-induced neurite outgrowth in N2a cells is regulated by cross-talk between the MEK/ERKs and PI3K/Akt pathways and requires the activation of the MEK/ERKs signaling.1. Biochim Biophys Acta. 2011 May;1813(5):827-38. doi: 10.1016/j.bbamcr.2011.01.027. Epub 2011 Feb 2. Essential role of ERK activation in neurite outgrowth induced by α-lipoic acid. Wang X, Wang Z, Yao Y, Li J, Zhang X, Li C, Cheng Y, Ding G, Liu L, Ding Z. Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China. BACKGROUND: Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. Alpha-lipoic acid (LA) has been used as a therapeutic approach for a variety of neural disorders. We recently reported that LA prevents local anesthetics-induced neurite loss. In this study, we hypothesized that LA administration promotes neurite outgrowth. METHODS: To test our hypothesis, we treated mouse neuroblastoma N2a cells and primary neurons with LA. Neurite outgrowth was evaluated by examination of morphological changes and by immunocytochemistry for β-tubulin-3. ROS production was examined, as were the phosphorylation levels of ERK and Akt. In separate experiments, we determined the effects of the inhibition of ERK or PI3K/Akt as well as ROS production on LA-induced neurite outgrowth. RESULTS: LA promoted significantly neurite outgrowth in a time- and concentration-dependent manner. LA stimulation significantly increased the phosphorylation levels of both Akt and ERK and transiently induced ROS production. PI3K/Akt inhibition did not affect LA-induced neurite outgrowth. However, the inhibition of ERK activation completely abolished LA-induced neurite outgrowth. Importantly, the prevention of ROS production by antioxidants attenuated LA-stimulated ERK activation and completely abolished LA-promoted neurite outgrowth. CONCLUSION: Our data suggest that LA stimulates neurite outgrowth through the activation of ERK signaling, an effect mediated through a ROS-dependent mechanism. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
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Originally Posted by ian
