1,721,008 research outputs found
Extending lifespan through autophagy stimulation: a future perspective
No full textAging is a natural process characterized by the gradual decline of physiological functions. In the last decades, human lifespan has considerably increased. Consequently, population aging and the resulting increase of people affected by age-related diseases, is emerging as a major social and economic challenge in developed countries. This scenario has led to an exponential growth of research projects in the field of aging, with the aim of identifying amenable drug targets and pharmacological interventions to extend human healthy lifespan. Extensive evidence in literature suggests that the dysfunction of autophagy, a highly conserved pathway involved in maintaining cellular homeostasis, is part of the aging process with roles in the pathobiology of age-related diseases. Moreover, accumulating experimental data from invertebrate and vertebrate animal models demonstrate that intervening to increase lifespan also induces autophagy, suggesting that stimulating such cellular process may represent an effective strategy to increase longevity. Here, we reviewed the literature on autophagy in aging and age-related diseases, also discussing the perspective of behavioral and pharmacological interventions that may increase healthy lifespan through autophagy stimulation
Intrathecal administration of mTOR inhibitors for the therapy of neurodegenerative, neuroinflammatory and neurooncologic diseases
No full textThe invention relates to the use of inhibitors of the enzyme mTOR kinase (mammalian target of rapamycin) in the treatment of neuro-oncol. diseases, in particular tuberous sclerosis, neurodegenerative diseases, in particular Alzheimer's disease, and neuroinflammatory diseases, in particular multiple sclerosis and primary progressive aphasia, via intrathecal, or preferably intraventricular, administration of said inhibitors. Thus, from the evidence presented in the disclosure, it was evident that it is possible to reaching locally, within the cranial theca, a concn. of inhibitor greater than that reached in the same region through systemic administration; from there it is concluded that the inhibitor present here is capable of inhibiting the mTOR signalling pathway; it is also seen that this concn. is capable of performing an immunosuppressive action locally, while remaining in the blood at unassayable levels and without affecting the normal activity of mTOR in peripheral organs
Jurkat T-cell stimulation up-regulates the expression of lysosomal β-hexosaminidase and β-galactosidase and triggers their recruitment to lipid microdomains
No full textIdentification and characterization of mature beta-hexosaminidases associated with human placenta lysosomal membrane
No full textHex (â-hexosaminidase) is a soluble glycohydrolase involved in glycoconjugate degradation in lysosomes, however its
localization has also been described in the cytosol and PM (plasma membrane). We previously demonstrated that
Hex associated with human fibroblast PM as the mature form, which is functionally active towards GM2 ganglioside.
In the present study, Hex was analysed in a lysosomal membrane-enriched fraction obtained by purification from
highly purified human placenta lysosomes. These results demonstrate the presence of mature Hex associated
with the lysosomal membrane and displaying, as observed for the PM-associated form, an acidic optimum pH.
When subjected to sodium carbonate extraction, the enzyme behaved as a peripheral membrane protein, whereas
Triton X-114 phase separation confirmed its partially hydrophilic nature, characteristics which are shared with the
PM-associated form of Hex. Moreover, two-dimensional electrophoresis indicated a slight difference in the pI of â-
subunits in the membrane and the soluble forms of the lysosomal Hex. These results reveal a new aspect of Hex
biology and suggest that a fully processed membrane-associated form of Hex is translocated from the lysosomal
membrane to the PM by an as yet unknown mechanism. We present a testable hypothesis that, at the cell surface,
Hex changes the composition of glycoconjugates that are known to be involved in intercellular communication and
signalling
Expression of the glycolytic enzymes enolase and lactate dehydrogenase during the early phase of Toxoplasma differentiation is regulated by an intron retention mechanism
Full text linkPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111944/1/mmi12999.pd
Identification and characterization of a fully processed beta-hexosaminidase isoform associated to lysosomal membrane-52° Congresso SIB
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