Interactions between Neurofilaments and L-dopa

Neurofilaments (NFs) are the primary structural components of neurons, and are found in high concentration along axons. They assemble into 10 nm diameter rods with radiating side arms from three subunit proteins of low (NF-L), medium (NF-M), and high (NF-H) molecular weights. Abnormal aggregation of NFs is a hallmark of several neurological disorders including Parkinson's disease, where tangles of NFs, called Lewy bodies, are a characteristic pathology. It was shown previously that a commonly prescribed drug to treat the symptoms of Parkinson's disease, L-dopa, will covalently crosslink NFs resulting in biochemically altered filamentous aggregates similar to Lewy bodies1. Here, we incubated the NFs, purified from bovine spinal cord, in the presence of L- dopa and analyzed them using SDS-PAGE to detect crosslinking. Low concentrations of NFs (<1.5mg/ml) incubated with and without L- dopa showed the characteristic NF subunit banding pattern suggesting that the NFs were not covalently crosslinked, contradicting previous reports1. At significantly higher NF concentrations, crosslinking was observed and we show that a critical protein concentration is needed for crosslinking to occur.

1. Montine, T.J. et al. Covalent Crosslinking of Neurofilament Proteins by Oxidated Catechols as a Potential Mechanism of Lewy Body formation. J. Neuropathology and Experimental Neurology, 54, 3, 311-319.