GDAP1 Activators

Ganglioside-induced differentiation-associated protein 1 (GDAP1) is a protein that has been implicated in the functioning of the peripheral nervous system. It is encoded by the GDAP1 gene. GDAP1 plays a critical role in the biology of Schwann cells, which are responsible for the myelination of neuronal axons in the peripheral nervous system, as well as in mitochondrial dynamics and energy metabolism.GDAP1 is predominantly located in the mitochondrial outer membrane, where it influences mitochondrial fission and fusion, processes that are essential for maintaining mitochondrial shape, distribution, and function. The balance of these processes is crucial for neuronal health, as neurons rely heavily on mitochondria for energy production and calcium buffering.

Mutations in the GDAP1 gene have been associated with several forms of Charcot-Marie-Tooth disease (CMT), which is a group of inherited neurological disorders that affect motor and sensory neurons. These mutations can cause both the axonal form of CMT (type 2) and the demyelinating form (type 4), leading to a wide range of presentations, from mild to severe neuropathy. The disease manifestations include muscle weakness, atrophy, and sensory loss, typically starting in the feet and legs and progressing over time.