Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Hutchinson-Gilford progeria syndrome (HGPS) is a very rare, but well known inherited condition of uncertain etiology in which features of premature and accelerated aging are mixed with those of delayed maturity and immaturity. Appearance at birth and birth weight are usually normal but growth typically slows after 1 year. All organ systems undergo degeneration to such an extent that the patient resembles an old man or woman. Short stature, micrognatia, alopecia, sculptured nose, prominent scalp veins, loss of subcutaneous fat, prominent joints, hyperlipidemia and early arteriosclerosis characterize the syndrome. Skeletal compromise includes hypoplasia and dysplasia, persistent open fontanelles, severe osteolysis and pathological fractures. There are no intellectual deficits in patients with this syndrome, and intelligence is unaffected. The life span in progeria is shortened by early arteriosclerosis. In this case, we review the characteristics of the severe osteolytic compromise in distal arms and limbs and bone deformities in a case of an 8-year-old girl, who was admitted to our hospital with short stature and loss of hair. On examination, the child had the major clinical criteria for HGPS as well as severe alterations in osteogenesis, including craniofacial disproportion, short and sculptured nose, delayed dentition, severe scoliosis, clavicular deformity and asymmetrical and hypoplastic arms and legs. Generalized osteopenia and severe osteolytic compromise in distal extremities were found by X-ray examination. In summary, we report the case of an 8-year-old girl who meets the diagnostic criteria for HGPS with severe involvement of her bones and joints with a review of the current literature and a possible therapeutic approach.
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PMID:Severe bone changes in a case of Hutchinson-Gilford syndrome. 1238 48

Understanding the interplay between reversible epigenetic changes and potentially more difficult to reverse accumulation of damaged macromolecules is a central challenge in developing treatments for aging-associated dysfunction. One hypothesis is that epigenetic drift leads to subtle losses of homeostatic maintenance mechanisms, that in turn, lead to the accumulation of damaged macromolecules, which then further degrade homeostasis. A key mechanism of maintaining optimal cell function is asymmetrical division, whereby cellular damage is segregated away from cells that need to undergo further proliferation, such as stem cells. Such asymmetrical distribution of damaged macromolecules has been observed during cell division in many organisms, from yeast to human embryonic stem cells, and depends on diffusion barriers (DBs) in the membrane of the endoplasmic reticulum (ER). In a recent study, these results have been extended to neural stem cells (NSCs), in which the ability of the ER DB to promote asymmetrical distribution of damaged proteins deteriorates with age. NSC function declines with age as proliferative capacity is reduced. The loss of asymmetric protein distribution correlates with the loss of NSC proliferative capacity. Ectopic expression of progerin, an altered form of lamin A, is associated with the premature aging disorder, Hutchinson-Gilford progeria syndrome (HGPS). Progerin's expression also increases with normal aging due to mis-splicing, weakening the ER DB. Recent work suggests that many cell signaling pathway changes associated with HGPS are replicated during normal aging in cultured cells. Moreover, the detrimental changes associated with progerin expression in HGPS are partially reversible experimentally after treatment with statins, a farnesyltransferase inhibitor, a isoprenylcysteine carboxyl methyltransferase inhibitor, or sulforaphane. It will be of great interest if these compounds can also reverse the aging-associated permeability of the ER DB and restore stem cell function.
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PMID:Aging Stem Cells Lose the Capability to Distribute Damaged Proteins Asymmetrically. 2665 Jun 79