Neuroscience

The cytoskeleton consists of three types of cytosolic fibers: actin microfilaments, intermediate filaments, and microtubules. Neurofilaments are the major intermediate filaments found in neurons and consist of light (NFL), medium (NFM), and heavy (NFH) subunits (1). Similar in structure to other intermediate filament proteins, neurofilaments have a globular amino-terminal head, a central α-helical rod domain, and a carboxy-terminal tail. A heterotetrameric unit (NFL-NFM and NFL-NFH) forms a protofilament, with eight protofilaments comprising the typical 10 nm intermediate filament (2). While neurofilaments are critical for radial axon growth and determine axon caliber, microtubules are involved in axon elongation. PKA phosphorylates the head domain of NFL and NFM to inhibit neurofilament assembly (3,4). Neurofilament accumulations are found in many human neurological disorders including Parkinson's disease (in Lewy bodies along with α-synuclein), Alzheimer's disease, Charcot-Marie-Tooth disease, and Amyotrophic Lateral Sclerosis (ALS) (1).

1. Al-Chalabi, A. and Miller, C.C. (2003) Bioessays 25, 346-355.
2. Cohlberg, J.A. et al. (1995) J. Biol. Chem. 270, 9334-9339.
3. Hisanaga, S. et al. (1994) Mol. Biol. Cell 5, 161-172.
4. Sihag, R.K. et al. (1999) J. Neurochem. 72, 491-499.

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Neurofilament-L Blocking Peptide

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