One age associated muscle disorder is due to mutations in valosin containing protein (VCP) which causes IBMPFD/ALS or inclusion body myopathy (IBM) associated with Paget's disease of the bone (PDB), fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Muscle weakness is the most prevalent phenotypic feature. Although IBMPFD itself is rare, the culmination of each component (IBM, PDB, FTD and ALS) makes its incidence more common in the general population. VCP mutations disrupt autophagosome maturation resulting in dysfunctional autophagy and muscle weakness. We propose to develop a methodology to quantitate autophagy in human skeletal muscle.
Pathologic protein inclusions accumulate in many divergent disease states associated with aging like inclusion body myositis and dementia. We hypothesis that an impairment in autophagy and autophagy signaling pathways conferred by mutations in the protein VCP result in inclusion body myopathy associated with paget's disease of the bone, fronto-temporal dementia and amyotrophic lateral sclerosis (IBMPFD/ALS). Understanding IBMPFD/ALS and autophagy will lend insight into the treatment of other more common age related disorders.
| Lee, YouJin; Jonson, Per Harald; Sarparanta, Jaakko et al. (2018) TIA1 variant drives myodegeneration in multisystem proteinopathy with SQSTM1 mutations. J Clin Invest 128:1164-1177 |
| Papadopoulos, Chrisovalantis; Kirchner, Philipp; Bug, Monika et al. (2017) VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy. EMBO J 36:135-150 |
| Güttsches, Anne-Katrin; Brady, Stefen; Krause, Kathryn et al. (2017) Proteomics of rimmed vacuoles define new risk allele in inclusion body myositis. Ann Neurol 81:227-239 |
| Lee, YouJin; Chou, Tsui-Fen; Pittman, Sara K et al. (2017) Keap1/Cullin3 Modulates p62/SQSTM1 Activity via UBA Domain Ubiquitination. Cell Rep 19:188-202 |
| Oh, Sung-Hee; Choi, Yong-Bok; Kim, June-Hyun et al. (2017) Comparisons of ELISA and Western blot assays for detection of autophagy flux. Data Brief 13:696-699 |
| Klionsky, Daniel J (see original citation for additional authors) (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12:1-222 |
| Bhattacharya, Martha R C; Geisler, Stefanie; Pittman, Sara K et al. (2016) TMEM184b Promotes Axon Degeneration and Neuromuscular Junction Maintenance. J Neurosci 36:4681-9 |
| Jerath, Nivedita U; Crockett, Cameron D; Moore, Steven A et al. (2015) Rare Manifestation of a c.290 C>T, p.Gly97Glu VCP Mutation. Case Rep Genet 2015:239167 |
| Bengoechea, Rocio; Pittman, Sara K; Tuck, Elizabeth P et al. (2015) Myofibrillar disruption and RNA-binding protein aggregation in a mouse model of limb-girdle muscular dystrophy 1D. Hum Mol Genet 24:6588-602 |
| Weihl, Conrad C; Baloh, Robert H; Lee, Youjin et al. (2015) Targeted sequencing and identification of genetic variants in sporadic inclusion body myositis. Neuromuscul Disord 25:289-96 |
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