Mechanisms of Neurotoxicity and Neuroprotection

Cannabidiol and THC reduced neurotoxicty induced by glutamate in cortical neurons (Hampson et al. 1998). This result was effective for toxicity induced at both NMDA and AMPA/kainate receptors, and was independent of cannabinoid receptor activity. The mechanism of neuroprotection appears to be by their potent antioxidant activity. They were even more protective against glutamate neurotoxicity than either ascorbate or o-tocopherol. 

Danysz W, Parsons CG, Mobius HJ, et al (2000) Neuroprotective and symptomatological action of memantine relevant for Alzheimer s disease—an unified glutamatergic hypothesis on the mechanism of action. Neurotox Res 2 85-97 Davis SM, Lees KR, Albers GW, et al (2000) Selfotel in acute ischemic stroke possible neurotoxic effects of an NMDA antagonist. Stroke 31 347-354 DeKeyser J (1991) Excitotoxic mechanisms may be involved in the pathophysiology of tardive dyskinesia. Clin Neuropharmacol 14 562-565 Del Dotto P, Pavese N, Gambaccini G, et al (2001) Intravenous amantadine improves levodopa-induced dyskinesias an acute double-blind placebo-controlled study. Mov Disord 16 515-520... 

Danysz W, Parsons CG, Mobius HJ, et al Neuroprotective and symptoma-logical action of memantine relevant for Alzheimer s disease—a unified glutamatergic hypothesis on the mechanism of action. Neurotox Res... 

The potential mechanism of action of the volatile anaesthetic agents and the evidence from animal and clinical studies on the effects on the nervous system, both neuroprotective and neurotoxic, have been reviewed [3 ]. The small number of clinical studies available and reviewed in the commentary supports both protective and toxic roles. 

In summary, FAEE protects neuronal cells and synaptosomes against oxidative stress and neurotoxicity as shown by a number of oxidative stress markers. We hypothesize a multifaceted mechanism by which FAEE offers neuroprotection on in vitro models of AD ... 

Alzheimer s, Parkinson s and prion diseases are characterized by neuronal loss and protein aggregates that may or may not be fibrillar. However, the exact identity of the neurotoxic species and the mechanism by which it kills neurons are unknown. Biophysical studies support the emerging notion that a prefibrillar oligomer (protofibril) may be responsible for cell death and that the fibrillar form that is typically observed post mortem may actually be neuroprotective. The laboratory of Peter Lansbury suggests that a subpopulation of the soluble protofibrils may function as pathogenic pores that might have the ability to permeabilize cell or mitochondrial membranes 35). Annular, pore-like structures are observed in familial mutants of a-synuclein (Parkinson s disease) and Alzheimer s precursor protein (Alzheimer s disease) as shown in Plate 3A 56). 

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