Chapter 11 - Immune-mediated cell death and neuroprotection in neurodegenerative diseases

Abstract

Selective neuronal injury and cell death are the traits of the neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinsons disease (PD), and Alzheimer's disease (AD). The clinical presentation of ALS has been well characterized as one of painless motor weakness, usually accompanied by lower motor neurone findings of denervation atrophy and motor fasciculations, and by upper motor neurone findings of spasticity and hyperactive reflexes. The autoimmune theory of ALS suggests that antibodies to a motor neurone antigen may constitute the primary event leading to motor neurone destruction. In phospholipid bilayers containing skeletal muscle nifedipine-sensitive L-type voltage-gated calcium channels (VGCCs), ALS immunoglobulin G (IgG) reduces the mean calcium channel open time and diminishes the amplitude of the calcium current. Increased intracellular calcium mediates neuronal cell death in ALS models. Immunological mechanisms, at least in ALS, and possibly in other neurodegenerative diseases, may initiate the neurone death cascade by targeting ion channels and enhancing calcium entry.