Impaired Intracellular Trafficking Is a Common Disease Mechanism ofPMP22Point Mutations in Peripheral Neuropathies

@article{Naef1999ImpairedIT,
  title={Impaired Intracellular Trafficking Is a Common Disease Mechanism ofPMP22Point Mutations in Peripheral Neuropathies},
  author={Roland Naef and Ueli Suter},
  journal={Neurobiology of Disease},
  year={1999},
  volume={6},
  pages={1-14}
}
The most common forms of hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth disease (CMT) are associated with mutations affecting myelin genes in the peripheral nervous system. A minor subgroup of CMT type 1A (CMT1A) is caused by point mutations in the gene encoding the peripheral myelin protein 22 (PMP22). To study the mechanisms by which these mutations cause the CMT pathology, we transiently transfected COS7 and Schwann cells with wild-type and PMP22 expression… 
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The PMP22 Gene and Its Related Diseases
TLDR
The basic genetics, biochemistry and molecular structure of PMP22 are reviewed, followed by discussion of the current understanding of pathogenic mechanisms involving in the inherited neuropathies with mutations in PMP 22 gene.
Recessive, but not dominant, mutations in peripheral myelin protein 22 gene show unique patterns of aggregation and intracellular trafficking
Alterations in degradative pathways and protein aggregation in a neuropathy model based on PMP22 overexpression
Phenotypic Differences between Peripheral Myelin Protein‐22 (PMP22) and Myelin Protein Zero (P0) Mutations Associated with Charcot‐Marie‐Tooth‐Related Diseases
TLDR
The studies indicate that different types of PMP22 and P0 mutations are associated with specific intracellular chaperone proteins, including calnexin and BiP, and that these associations can be altered by glycosylation.
Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease
TLDR
The putative functions and malfunctions of proteins encoded by genes mutated in Charcot-Marie-Tooth disease (CMT; inherited motor and sensory neuropathies) in normal and affected peripheral nerves are reviewed to delineate the detailed molecular functions of the proteins associated with CMT in health and disease.
Molecular alterations resulting from frameshift mutations in peripheral myelin protein 22: Implications for neuropathy severity
TLDR
Results suggest that a greater potential for PMP22 aggregation is associated with a less severe phenotype, whereas dysregulation of Schwann cell proliferation is linked to severe neuropathy.
Cellular mechanisms of connexin32 mutations associated with CNS manifestations
TLDR
Results indicate that Cx32 mutants that are associated with a CNS phenotype do not interact with Cx45, but may instead have other toxic effects in oligodendrocytes.
Identification of a New Pmp22 Mouse Mutant and Trafficking Analysis of a Pmp22 Allelic Series Suggesting That Protein Aggregates May Be Protective in Pmp22-Associated Peripheral Neuropathy
TLDR
It is shown that each mutant protein in the allelic series has a unique pattern of intracellular localization in transfected cell lines, and suggests that large Pmp22 aggregates may be protective in this form of peripheral neuropathy.
Molecular basis of inherited neuropathies.
TLDR
Overexpression or underexpression of peripheral myelin protein of 22 kDa are causative for the most frequent forms of CMT-CMT1A and hereditary neuropathy with liability to pressure palsies--but the mechanisms that lead to incorrect myelin formation and maintenance are still unknown.
Mutations associated with Charcot–Marie–Tooth disease cause SIMPLE protein mislocalization and degradation by the proteasome and aggresome–autophagy pathways
TLDR
SIMPLE is an early endosomal membrane protein that is highly expressed in the peripheral nerves and Schwann cells and the analysis has identified a transmembrane domain (TMD) embedded within the cysteine-rich (C-rich) region that anchors SIMPLE to the membrane, and suggests that SIMPLE is a post-translationally inserted, C-tail-anchored membrane protein.
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References

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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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