| Peripherin | |
|---|---|
| Gene | [PRPH](/genes/prph) |
| UniProt ID | P17656 |
| Molecular Weight | ~57 kDa |
| Subcellular Localization | Cytoplasm, Neuronal intermediate filaments |
| Protein Family | Intermediate filament protein family |
| Structure | Alpha-helical coiled-coil rod domain |
Peripherin Protein is a protein encoded by the PRPH gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Peripherin is a type III intermediate filament protein composed of an N-terminal head domain, a central alpha-helical rod domain, and a C-terminal tail domain[1]. The rod domain contains conserved coiled-coil motifs that facilitate dimerization and higher-order assembly into filamentous structures[2]. Unlike other type III IF proteins, peripherin has a unique C-terminal tail with a variable region that may confer neuron-specific assembly properties[3].
Peripherin is primarily expressed in peripheral neurons and a subset of central nervous system neurons[4]. It plays critical roles in:
Peripherin is implicated in ALS pathogenesis through several mechanisms[9]:
While primarily studied in ALS, peripherin interactions with tau and other cytoskeletal proteins suggest potential roles in AD pathogenesis[14]. Peripherin can form heteropolymers with tau, potentially modulating tau aggregation kinetics and neurotoxicity.
Current therapeutic approaches targeting peripherin-related pathways include[15]:
| Approach | Status | Mechanism |
|---|---|---|
| Gene silencing | Preclinical | siRNA/shRNA targeting mutant PRPH transcripts |
| Protein aggregation inhibitors | Preclinical | Small molecules preventing IF aggregation |
| Autophagy enhancement | Preclinical | mTOR-independent autophagy inducers |
| Neuroprotective small molecules | Preclinical | Cytoskeletal stabilizing agents |
Steinert PM, et al. The coiled-coil rod domain of intermediate filament proteins. Journal of Molecular Biology. 1985. ↩︎
Parry DA, et al. Intermediate filament proteins. Trends in Cell Biology. 2005. ↩︎
Cote F, et al. Peripherin, a novel intermediate filament protein. Developmental Biology. 1989. ↩︎
Portier MM, et al. Peripherin, a neuronal intermediate filament protein. Neuropathology and Applied Neurobiology. 1993. ↩︎
Nixon RA, et al. The role of intermediate filaments in neuronal development and disease. Journal of Neuropathology & Experimental Neurology. 2000. ↩︎
Shea TB, et al. Dynein mediates neurofilament transport. Journal of Neurochemistry. 1989. ↩︎
Parhad IM, et al. Localization of peripherin in synapses. Brain Research. 1995. ↩︎
Elder GA, et al. Intermediate filament dysfunction in neurodegenerative diseases. Neurobiology of Disease. 1998. ↩︎
Beaulieu JM, et al. Peripherin and ALS. Experimental Neurology. 1999. ↩︎
Matsuoka G, et al. Peripherin aggregates in ALS motor neurons. Brain Research. 2001. ↩︎
Xiao S, et al. Peripherin mutations cause progressive motor neuron degeneration. Brain. 2006. ↩︎
Cheung PY, et al. ER stress in peripherin-mediated neurodegeneration. Cell Death & Disease. 2014. ↩︎
Song F, et al. Selective vulnerability of peripheral neurons. Neurobiology of Disease. 2009. ↩︎
Zhang YJ, et al. Tau-peripherin interactions. Acta Neuropathologica. 2015. ↩︎
Pagano M, et al. Targeting intermediate filaments in neurodegenerative diseases. Trends in Pharmacological Sciences. 2020. ↩︎