Local Anesthetic Procaine Protects Rat Pheochromocytoma PC12 Cells against β-Amyloid-Induced Neurotoxicity

Abstract

Alzheimer’s disease (AD) is the most common dementia occurring in elderly. We report herein the neuroprotective properties of procaine and other anesthetic agents against β-amyloid-induced neurotoxicity. Procaine displayed strong neuroprotective properties against the amyloid peptide Aβ_1–42 and preserved Aβ_1–42-induced ATP depletion on rat pheochromocytoma PC12 cells. Procaine also inhibited the neurotoxic effect that glutamate displayed on PC12 cells, suggesting that the reduction of glutamate-induced neurotoxicity may be the mechanism by which these compounds exert their ‘antiamyloid’ effects. In search of a mechanism of action we observed that procaine is a ligand for the σ1 receptor, a protein which ligands have been shown to protect mitochondrial function and to exert antidepressant properties. Procaine binds also to muscarinic receptors but the true meaning of this feature needs to be clarified. In conclusion, these data suggest that procaine exerts neuroprotective properties and may serve either as a treatment for AD or as a starting point for the development of novel therapies for AD.

Healthy Aging

“…Procaine has known neuroprotective properties, preventing the formation of amyloid plaques and preserving ATP depletion, most likely by inhibiting neurotoxic effect of glutamate, like has been shown in PC12 rat cells cultures [76].…”

Procaine–The Controversial Geroprotector Candidate: New Insights Regarding Its Molecular and Cellular Effects

“…Numerous beneficial actions were reported for procaine concerning the CNS, beyond its anesthetic effect. Experimental studies highlighted neuroprotective, antidepressant, and “anti-amyloid” actions [ 116 ], along inhibition of JAK2 and STAT3 expression in neuropathic pain models [ 117 ]. The inhibitory effect on MAO-B of procaine-derivatives, as well as the in vivo anti-Parkinson effect, was associated with lower levels of mitochondrial lipid peroxidation and improved levels of antioxidant enzymes in the striatum [ 37 ] ( Table 4 ).…”

“…Procaine also displayed strong neuroprotective properties against the amyloid peptide A β 1-42 and preserved A β 1-42 -induced ATP depletion. Procaine inhibited the neurotoxic effect of glutamate on PC12 cells, suggesting that the reduction of glutamate-induced neurotoxicity may be the mechanism by which procaine exert its “anti-amyloid” effect [ 116 ]. Li et al (2016) studied the effect of procaine treatment in a rat model of neuropathic pain.…”

Clinical efficacy of neural therapy for the treatment of atopic dermatitis in dogs

“…Procaine is the least neurotoxic agent of all clinically used local anaesthetics (Kasaba et al, 2003), and it even possesses neuroprotective properties (Lecanu et al, 2005). The only contraindication for the use of NT with procaine is in cases when allergy to procaine can be forecasted.…”