Possible involvement of neuronal nicotinic acetylcholine receptors in compensatory brain mechanisms at early stages of Parkinson's disease

Abstract

A role of nicotinic acetylcholine receptors (nAChR) in the development of Parkinson's disease (PD) has been investigated using two mouse models corresponding to the presymptomatic stage and the early symptomatic stage of PD. Quantitative determination of nAChR in the striatum and substantia nigra (SN) was performed using the radioactive derivatives of epibatidine, -conotoxin MII, and -bungarotoxin as ligands. The number of ligand-binding sites changed differently depending on their location in the brain, the stage of the disease and the receptor subtype. Epibatidine binding decreased in the striatum to 66% and 70% at the presymptomatic and early symptomatic stages, respectively, whereas in SN a 160% increase was registered at the presymptomatic stage. The -conotoxin MII binding on striatal dopaminergic axonal terminals at the presymptomatic stage decreased by 20% and at the symptomatic stage it demonstrated a further decrease. The increase in -bungarotoxin binding at the presymptomatic stage and a decrease at the early symptomatic stage was observed in the striatum. In SN, the level of -bungarotoxin binding decreased at the presymptomatic stage and kept constant at the symptomatic stage. The significant decrease in the expression of Chrna4 and Chrna6 genes encoding 4 and 6 nAChR subunits was observed in SN at the early symptomatic stage, while a 13-fold increase in expression of the Chrna7 gene encoding the 7 nAChR subunit was detected at the presymptomatic stage. The data obtained suggest possible involvement of nAChR in compensatory mechanisms at early PD stages.

Proteomic Investigations of Two Pakistani Naja Snake Venoms Species Unravel the Venom Complexity, Posttranslational Modifications, and Presence of Extracellular Vesicles

“…Investigating 3FTXs are not only of interest to characterize their toxicity, but also of great significance for structural studies, as well as for biotechnological, biomedical and evolutionary studies [ 59 , 60 , 61 , 62 , 63 ]. Already, 3FTXs have proven to be an efficient tool to analyze various receptor types, and to study diseases like Parkinson’s disease, myasthenia gravis and cancer [ 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. The aminergic toxins from mamba venom served as good candidates for protein resurrection methodology [ 72 ].…”

Snake Venom Peptides: Tools of Biodiscovery

“…Mutation of the invariant Cys-loop Asp residue, in the acetylcholine receptor δ-subunit was identified in a patient suffering from congenital myasthenia syndrome [ 77 ]. A recent study employing the use of radioactive derivative of α-bungarotoxin suggested the possible function of neuronal nAChR in the development of Parkinson’s disease [ 78 ]. Apart from serving as molecular probes in various medical disorders, three-finger neurotoxins are also gaining attention as potential analgesics, anti-inflammatory molecules, and immunosuppressant [ 79 ].…”