HSPB1

The HSPB1 gene provides instructions for making a protein called heat shock protein beta-1 (also called heat shock protein 27). This protein is a member of the heat shock protein family, which helps to protect cells under adverse conditions such as infection, inflammation, exposure to toxins, elevated temperature, injury, and disease. Heat shock proteins block signals that tell cells to self-destruct through a sequence of events known as programmed cell death (apoptosis). Heat shock proteins also appear to be involved in activities such as cell motility and muscle movement, stabilizing the cell's structural framework (the cytoskeleton), assisting with folding and stabilizing newly produced proteins, and repairing damaged proteins.

Heat shock protein beta-1 is found in cells throughout the body and is abundant in nerve cells. In nerve cells, this protein helps to organize a network of molecular threads called neurofilaments that maintain the diameter of specialized extensions called axons. Maintaining proper axon diameter is essential for the efficient transmission of nerve impulses.

Charcot-Marie-Tooth disease - caused by mutations in the HSPB1 gene

Three HSPB1 mutations have been reported in individuals with a form of Charcot-Marie-Tooth disease known as type 2F. Each mutation changes a single protein building block (amino acid) used to make heat shock protein beta-1. One mutation replaces the amino acid serine with the amino acid phenylalanine at protein position 135 (written as Ser135Phe). The other mutations replace the amino acid arginine with the amino acid tryptophan at position 136 (Arg136Trp) or at position 127 (Arg127Trp). These mutations alter a region of the protein that is critical for heat shock protein beta-1 to function properly.

It is unclear how HSPB1 mutations lead to axon abnormalities that are characteristic of type 2F Charcot-Marie-Tooth disease. Researchers suggest that molecules of altered heat shock protein beta-1 cluster together (aggregate) and interfere with the normal functions of nerves cells, particularly axons. Another possibility is that the altered protein disrupts the assembly of neurofilaments, which affects axon diameter and impairs the transmission of nerve impulses.

other disorders - caused by mutations in the HSPB1 gene

Researchers have identified several HSPB1 mutations that cause a condition called distal hereditary motor neuropathy, which is similar to Charcot-Marie-Tooth disease. Distal hereditary motor neuropathy affects peripheral nerves, which connect the brain and spinal cord to muscles. The disorder is characterized by progressive weakness in the feet and hands. Unlike Charcot-Marie-Tooth disease, however, distal hereditary motor neuropathy does not affect sensory cells that detect sensations such as touch, sound, and sight.

Each HSPB1 mutation replaces one of the protein building blocks (amino acids) in heat shock protein beta-1 with an incorrect amino acid. It is unclear how HSPB1 mutations lead to axon abnormalities that are characteristic of distal hereditary motor neuropathy. Research findings suggest that molecules of altered heat shock protein beta-1 cluster together (aggregate) and block the transport of substances that are essential for the proper function of nerve axons. Another possibility is that the altered protein disrupts the assembly of neurofilaments, which disturbs axon diameter and impairs the transmission of nerve impulses .