Cell death in the nervous system

  • Article
    | Open Access

    Hyperphosphorylated Tau accumulation promotes neurodegeneration in Alzheimer’s disease. Here, the authors screen a miRNA library in Drosophila and identify a conserved ubiquitin ligase that directs Tau for autophagic degradation, uncovering a potential target to treat Tau-mediated neurodegeneration.

    • Manivannan Subramanian
    • , Seung Jae Hyeon
    •  & Kweon Yu
  • Article
    | Open Access

    During embryonic development, neural progenitor cells undergo numerous cell divisions. Here, the authors show that ABHD4-mediated developmental anoikis distinguishes the physiological delamination and the pathological detachment of progenitor cells with relevance to fetal alcohol-induced apoptosis.

    • Zsófia I. László
    • , Zsolt Lele
    •  & István Katona
  • Article
    | Open Access

    Small molecule polyamines participate in diverse aspects of cell growth and differentiation and are known to regulate ion channel gating. Here authors reveal that cellular polyamines control nicotinic acetylcholine receptor (nAChR) biogenesis, and either catabolic degradation or inhibition of polyamine production augments nAChR assembly.

    • Madhurima Dhara
    • , Jose A. Matta
    •  & David S. Bredt
  • Article
    | Open Access

    Calvo-Rodriguez et al. show elevated calcium levels in neuronal mitochondria in a mouse model of cerebral β-amyloidosis after plaque deposition, which precede rare neuron death events in this model. The mechanism involves toxic extracellular Aβ oligomers and the mitochondrial calcium uniporter.

    • Maria Calvo-Rodriguez
    • , Steven S. Hou
    •  & Brian J. Bacskai
  • Article
    | Open Access

    Voltage-gated Ca2+ channels are thought to contribute to neurodegeneration of dopaminergic neurons. Here the authors find that the R-type channel Cav2.3 in substantia nigra dopaminergic neurons may contribute to neurodegeneration in a model of Parkinson’s disease, in contrast to the neuroprotective action of the neuronal Ca2+ sensor NCS-1.

    • Julia Benkert
    • , Simon Hess
    •  & Birgit Liss
  • Article
    | Open Access

    During cortical development the first wave of oligodendrocyte precursor cells (OPCs) completely disappear by programmed cell death, so that it is presumed that this OPC population does not play a role at postnatal stages. In this study, authors use lineage tracing in different transgenic mice to show that a subpopulation of OPCs from the first wave survives at postnatal stages and display a preferential synaptic connectivity with their ontogenetically-related interneurons compared to other OPCs or interneurons

    • David Orduz
    • , Najate Benamer
    •  & María Cecilia Angulo
  • Article
    | Open Access

    To understand the molecular processes that link Aβ amyloidosis, tauopathy and neurodegeneration, the authors screened for tau-interacting proteins. They demonstrated that a novel tau binding protein CAPON accelerates tau pathology and neuronal cell death in an Alzheimer’s disease mouse model.

    • Shoko Hashimoto
    • , Yukio Matsuba
    •  & Takashi Saito
  • Article
    | Open Access

    It is unclear if neuromelanin plays a role in Parkinson’s disease pathogenesis since common laboratory animals lack this pigment. Authors show here that overexpression of human tyrosinase in the substantia nigra of rats resulted in an age-dependent production of human-like neuromelanin within nigral dopaminergic neurons and is associated with a Parkinson’s disease phenotype when allowed to accumulate above a specific threshold.

    • Iria Carballo-Carbajal
    • , Ariadna Laguna
    •  & Miquel Vila
  • Article
    | Open Access

    Impairment of DNA repair has been associated with neurodegeneration. Here the authors investigate the mechanisms of defects in repair caused by mutations in the RNA/DNA binding protein FUS in amyotrophic lateral sclerosis and elucidate its role in the DNA ligation during DNA single-strand break repair of oxidative breaks.

    • Haibo Wang
    • , Wenting Guo
    •  & Muralidhar L. Hegde
  • Article
    | Open Access

    Excitotoxicity contributes to neuronal injury following stroke. Here the authors show that tau promotes excitotoxicity by a post-synaptic mechanism, involving site-specific control of ERK activation, in a mouse model of stroke.

    • Mian Bi
    • , Amadeus Gladbach
    •  & Lars M. Ittner
  • Article
    | Open Access

    Investigating cell death in living organisms is hampered by a lack of techniques to induce apoptosis with spatial and temporal precision without collateral damage. Here the authors develop two-photon chemical apoptotic targeted ablation (2Phatal), allowing studies of apoptosis and its functional consequencesin vivo.

    • Robert A. Hill
    • , Eyiyemisi C. Damisah
    •  & Jaime Grutzendler
  • Article
    | Open Access

    Mutations inCHCHD10 have been recently associated with frontotemporal dementia and amyotrophic lateral sclerosis. Here the authors study the functions of endogenous CHCHD10 in Caenorhabditis elegans, primary neurons, and mouse, and show that it normally protects mitochondria and synaptic integrity, and retains TDP-43 in the nucleus.

    • Jung-A. A. Woo
    • , Tian Liu
    •  & David E. Kang
  • Article
    | Open Access

    Alexander disease is a rare neurological disorder caused by mutations in GFAP, yet it is unclear how glial disruptions lead to neural death. Here, Wang et al. identify a mechanism by which glial-derived nitric oxide leads to neuronal degeneration in fly and mouse models of the disease.

    • Liqun Wang
    • , Tracy L. Hagemann
    •  & Mel B. Feany
  • Article |

    TAR DNA-binding protein of 43 kDa (TDP-43) and its C-terminal fragment of 25 kDa (CTF25) play critical roles in several neurodegenerative diseases but the cleavage site that generates CTF25 remains undetermined. Here the authors show that caspase-4 cleaves TDP-43 after Aps174 generating CTF25, and this leads to TDP-43 clearance and increased cell viability.

    • Quan Li
    • , Moe Yokoshi
    •  & Yukio Kawahara
  • Article |

    Uncontrolled calcium release from the endoplasmic reticulum results in cell death and toxicity. Here, the authors show that in neurons, stress induces the export of receptor-interacting protein 140 from the nucleus to the cytosol where it interacts with IP3Receptor, preventing its opening and the detrimental effects of calcium release.

    • Xudong Feng
    • , Kelly A. Krogh
    •  & Li-Na Wei
  • Article |

    The removal of dying neurons by microglia plays a key role in both vertebrate nervous system development and several diseases. Here, the authors use a quantitative live imaging approach to investigate neuronal-microglial interactions at single-cell resolution and establish the functions of the phosphatidylserine receptors, TIM-4 and BAI1, in neuronal engulfment.

    • Fargol Mazaheri
    • , Oksana Breus
    •  & Francesca Peri