Neuronal intermediate filaments and neurodegenerative disorders

Neurofilaments at a glance

“…In some pathological conditions, neurofilaments can accumulate in large numbers within cell bodies and proximal axons of affected neurons (Liu et al, 2009;Munoz et al, 1988). In patients with amyotrophic lateral sclerosis (ALS), these accumulations are a hallmark pathological lesion, but they are also prominent in sufferers of other neurological diseases, such as CharcotMarie-Tooth (CMT) disease, neurofilament inclusion disease (NFID), giant axonal neuropathy (GAN), diabetic neuropathy, spinal muscular atrophy (SMA) and spastic paraplegia, and are present in those people that suffer from Alzheimer's disease (AD) and Parkinson's disease (PD) (Abe et al, 2009;Perrot and Eyer, 2009;Szaro and Strong, 2010). Transgenic mouse models support the idea that these aberrant NF accumulations contribute to the death of the affected neurons, rather than simply being by-products of the pathogenic process (Côté et al, 1993;Couillard-Després et al, 1998;Williamson et al, 1998).…”

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

“…Research over the years has unraveled various mechanisms or cellular components responsible for sensing mechanical stimuli in neurons: (i) the viscoelastic plasma membrane that consists of a 3 phospholipid bilayer that shows frequency dependent changes in tension and viscosity (Maxwell material) in response to mechanical stimuli that can trigger conformational changes in mechanosensitive ion channels, 19 (ii) the polymerization and de-polymerization of actin monomers into polymers 20 that is implicated in axonal growth cone dynamics 21 and dendritic spine plasticity, 22 (iii) microtubules that can generate forces via polymerization of αβ-tubulin dimers or catastrophic de-polymerization that can influence intracellular cargo transport and dendritic spine morphology, 23 (iv) neuro-filaments which are abundant cytoskeletal proteins in myelinated axons 24 that are proposed to provide mechanical protection to the brain against compressive loads such as during injury 25 and (v) the extracellular matrix and cell adhesion molecules that provide a mechanical framework for cellular growth and can influence signal transduction. 26 As the mechanisms for mechanical stimuli sensing in neurons are not the focus of this review, we refer the readers to Tyler et al 4 and Tsunozaki and Bautista 27 for a more comprehensive overview of this topic.…”

Viral interactions with intermediate filaments: Paths less explored

“…NFs are synthesized in the neuronal cell body and are transported to axons by virtue of the microtubule transport system. Initially it was thought that the contribution of NFs 15 Also, mutant NFs perturb the mitochondrial localization in neurons. Such an event is especially significant because, mitochondrial energy provision is clearly of the utmost importance in neuronal functioning.…”