Multisystem proteinopathy

Multisystem proteinopathy (MSP) is dominantly inherited, pleiotropic, degenerative disorder of humans that can affect muscle, bone and/or the central nervous system.[1] MSP can manifest clinically as classical amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), inclusion body myopathy (IBM), Paget's disease of bone (PDB), or as a combination of these disorders.[2] A useful operational definition of MSP is dominantly inherited degeneration that includes neurological involvement (either motor neuron disease or dementia) in combination with either distal myopathy or Pagetic bone degeneration. Most MSP patients present with weakness and of these ~65% present with motor neuron involvement.[2] Up to 30% of MSP patients may have exclusively motor neuron involvement.[2] 50% of MSP has been linked to missense mutations affecting the valosin-containing protein (VCP) gene.[3] Additional genes linked to MSP include HNRNPA1, HNRNPA2B1, HNRNPDL, MATR3, DNAJB6, OPTN, and p62/SQSTM1. The histopathology of tissues affected by MSP include ubiquitin-positive cytoplasmic inclusions of RNA-binding proteins, such as TDP-43, hnRNPA1, hnRNPA2B1, and other components of RNA granules.[4]

References

  1. ↑ Kim HJ, Kim NC, Wang YD et al. (March 2013). "Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS". Nature 495 (7442): 467–73. doi:10.1038/nature11922. PMC 3756911. PMID 23455423.
  2. ↑ 2.0 2.1 2.2 Benatar M, Wuu J, Fernandez C et al. (May 2013). "Motor neuron involvement in multisystem proteinopathy: implications for ALS". Neurology 80 (20): 1874–80. doi:10.1212/WNL.0b013e3182929fc3. PMC 3908355. PMID 23635965.
  3. ↑ Le Ber I, Van Bortel I, Nicolas G et al. (April 2014). "hnRNPA2B1 and hnRNPA1 mutations are rare in patients with 'multisystem proteinopathy' and frontotemporal lobar degeneration phenotypes". Neurobiology of Aging 35 (4): 934.e5–6. doi:10.1016/j.neurobiolaging.2013.09.016. PMID 24119545.
  4. ↑ Ramaswami M, Taylor JP, Parker R (August 2013). "Altered ribostasis: RNA-protein granules in degenerative disorders". Cell 154 (4): 727–36. doi:10.1016/j.cell.2013.07.038. PMC 3811119. PMID 23953108.