HSPB8

The HSPB8 gene provides instructions for making a protein called heat shock protein beta-8 (also called heat shock protein 22). This protein is a member of the heat shock protein family, which helps protect cells under adverse conditions such as infection, inflammation, exposure to toxins, elevated temperature, injury, and disease. Heat shock proteins block signals that lead to programmed cell death. In addition, they appear to be involved in activities such as cell movement (motility), stabilizing the cell's structural framework (the cytoskeleton), folding and stabilizing newly produced proteins, and repairing damaged proteins. Heat shock proteins also appear to play a role in the tensing of muscle fibers (muscle contraction).

Heat shock protein beta-8 is found in cells throughout the body and is particularly abundant in nerve cells. While its function is not well understood, it seems to interact with a related protein called heat shock protein beta-1, produced from the HSPB1 gene. In nerve cells, heat shock protein beta-1 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. The specific role that heat shock protein beta-8 plays in axons is unclear.

Charcot-Marie-Tooth disease - caused by mutations in the HSPB8 gene

A mutation in the HSPB8 gene has been reported in more than a dozen individuals in a large Chinese family with a form of Charcot-Marie-Tooth disease known as type 2L. Charcot-Marie-Tooth disease is a group of progressive disorders that affect the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.

The HSPB8 gene mutation that causes Charcot-Marie-Tooth disease changes the protein building block (amino acid) lysine to the amino acid asparagine at protein position 141, written as Lys141Asn or K141N.

It is unclear how HSPB8 gene mutations lead to the signs and symptoms of Charcot-Marie-Tooth disease, type 2L. Research suggests that the altered heat shock protein beta-8 interacts more strongly with heat shock protein beta-1 and is more likely to form clumps (aggregates). The aggregates may block the transport of substances that are essential for the proper function of nerve axons.

distal hereditary motor neuropathy, type II - caused by mutations in the HSPB8 gene

Researchers have identified at least two HSPB8 gene mutations that cause a condition called distal hereditary motor neuropathy, type II, which is similar to Charcot-Marie-Tooth disease. Distal hereditary motor neuropathy, type II affects peripheral nerves and is characterized by progressive weakness, primarily in the feet and legs. Unlike Charcot-Marie-Tooth disease, distal hereditary motor neuropathy, type II does not affect sensory cells.

One of the HSPB8 gene mutations that causes distal hereditary motor neuropathy, type II (Lys141Asn or K141N) is also associated with Charcot-Marie-Tooth disease, type 2L. Another mutation replaces the lysine in the same position with glutamic acid (written as Lys141Glu or K141E) and seems to increase protein aggregation in the same way. It is not well understood why the same HSPB8 gene mutation can cause either disorder. Researchers suggest that different distributions of protein aggregates within the peripheral nerves may result in different patterns of signs and symptoms. The disruption of other cell functions in which this protein is involved may also contribute to peripheral nerve disease.