Autophagy impairment: a crossroad between neurodegeneration and tauopathies

mTOR signaling in aging and neurodegeneration: At the crossroad between metabolism dysfunction and impairment of autophagy.

Compelling evidence indicates that the mammalian target of rapamycin (mTOR) signaling pathway is involved in cellular senescence, organismal aging and age-dependent diseases. mTOR is a conserved serine/threonine kinase that is known to be part of two different protein complexes: mTORC1 and mTORC2, which differ in some components and in upstream and downstream signalling. In multicellular organi...

Universidade de Lisboa Faculdade de Ciências SIRT2: in the crossroad of aging, neurodegeneration and autophagy

Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease.

Lafora disease is a fatal neurodegenerative condition characterized by the accumulation of abnormal glycogen inclusions known as Lafora bodies. It is an autosomal recessive disorder caused by mutations in either the laforin or malin gene. To study whether glycogen is primarily responsible for the neurodegeneration in Lafora disease, we generated malin knockout mice with impaired (totally or par...

Lamin Dysfunction Mediates Neurodegeneration in Tauopathies

The filamentous meshwork formed by the lamin nucleoskeleton provides a scaffold for the anchoring of highly condensed heterochromatic DNA to the nuclear envelope, thereby establishing the three-dimensional architecture of the genome [1]. Insight into the importance of lamins to cellular viability can be gleaned from laminopathies, severe disorders caused by mutations in genes encoding lamins. A...

Autophagy in neurodegeneration and development

Efficient protein turnover is essential for the maintenance of cellular health. Here we review how autophagy has fundamental functions in cellular homeostasis and possible uses as a therapeutic strategy for neurodegenerative diseases associated with intracytosolic aggregate formation, like Huntington's disease (HD). Drugs like rapamycin, that induce autophagy, increase the clearance of mutant h...