The Role of Autophagy in Mammalian Development: Cell Makeover Rather than Cell Death

Dulbecco Telethon Institute at the Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
Developmental Cell (Impact Factor: 10.37). 10/2008; 15(3):344-57. DOI: 10.1016/j.devcel.2008.08.012
Source: PubMed

ABSTRACT Autophagy is important for the degradation of bulk cytoplasm, long-lived proteins, and entire organelles. In lower eukaryotes, autophagy functions as a cell death mechanism or as a stress response during development. However, autophagy's significance in vertebrate development, and the role (if any) of vertebrate-specific factors in its regulation, remains unexplained. Through careful analysis of the current autophagy gene mutant mouse models, we propose that in mammals, autophagy may be involved in specific cytosolic rearrangements needed for proliferation, death, and differentiation during embryogenesis and postnatal development. Thus, autophagy is a process of cytosolic "renovation," crucial in cell fate decisions.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the progressive loss of articular cartilage, remodeling of the subchondral bone, and synovial inflammation. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that controls critical cellular processes such as growth, proliferation, and protein synthesis. Recent studies suggest that mTOR plays a vital role in cartilage growth and development and in altering the articular cartilage homeostasis as well as contributing to the process of cartilage degeneration associated with OA. Both pharmacological inhibition and genetic deletion of mTOR have been shown to reduce the severity of OA in preclinical mouse models. In this review article, we discuss the roles of mTOR in cartilage development, in maintaining articular cartilage homeostasis, and its potential as an OA therapeutic target.
    Drugs in R & D 02/2015; 15(1). DOI:10.1007/s40268-015-0082-z · 1.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multiple sclerosis (MS) has been associated with a history of sub-optimal exposure to ultraviolet light, implicating vitamin D3 as a possible protective agent. We evaluated whether 1,25(OH)2D3 attenuates the progression of experimental autoimmune encephalomyelitis (EAE), and explored its potential mechanisms. EAE was induced in C57BL/6 mice via immunization with MOG35-55, and some mice received 1,25(OH)2D3. 1,25(OH)2D3 inhibited EAE progression. Additionally, 1,25(OH)2D3 reduced inflammation, demyelination, and neuron loss in the spinal cord. The protective effect of 1,25(OH)2D3 was associated with significantly elevated expression of Beclin1, increased Bcl-2/Bax ratio, and decreased LC3-II accumulation. Thus, 1,25(OH)2D3 may represent a promising new MS treatment. Copyright © 2015 Elsevier B.V. All rights reserved.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways. In this review, we will highlight the anatomical structure of human and mouse cerebellum, the cellular composition of developing cerebellum, and the underlying gene expression programs involved in cell fate commitments in the cerebellum. A critical evaluation of the cell death literature suggests that apoptosis occurs in ~5% of cerebellar cells, most shortly after mitosis. Apoptosis and cellular autophagy likely play significant roles in cerebellar development, we provide a comprehensive discussion of their role in cerebellar development and organization. We also address the possible function of unfolded protein response in regulation of cerebellar neurogenesis. We discuss recent advancements in understanding the epigenetic signature of cerebellar compartments and possible connections between DNA methylation, microRNAs and cerebellar neurodegeneration. Finally, we discuss genetic diseases associated with cerebellar dysfunction and their role in the aging cerebellum.
    Frontiers in Cellular Neuroscience 01/2015; 8(450):1-26. DOI:10.3389/fncel.2014.00450 · 4.18 Impact Factor

Full-text (2 Sources)

Available from
Dec 24, 2014