Pozueta et al. NATURE COMMUNICATIONS | 4:1939 | DOI: 10.1038/ncomms2927 (Impact Factor 14.7)

Caspases have critical roles in Alzheimer’s disease pathogenesis. Here we show that caspase-2 is required for the cognitive decline seen in human amyloid precursor protein transgenic mice (J20). The age-related changes in behaviour and dendritic spine density observed in these mice are absent when they lack caspase-2, in spite of similar levels of amyloid beta (Ab) deposition and inflammation.(...)

Bosc et al. Cell Death and Disease (2022) 13:959 (Impact Factor 8.1)

Caspase-2 (Casp2) is a promising therapeutic target in several human diseases, including nonalcoholic steatohepatitis (NASH) and Alzheimer’s disease (AD). However, the design of an active-site-directed inhibitor selective to individual caspase family members is challenging because caspases have extremely similar active sites. Here we present new peptidomimetics derived from the VDVAD pentapeptide structure, harboring non-natural modifications at the P2 position and an irreversible warhead. (...)

Chauvier et al. Cell Death and Disease (2011) (Impact Factor 8.1)

Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia–ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters.(...)

Carlsson et al. ANN NEUROL 2011;00:000–000 (Impact Factor 8.1)

Perinatal brain injury is a major cause of neurodevelopmental handicaps. Multiple pathways of oxidant stress, inflammation, and excitotoxicity lead to cell damage and death, including caspase-dependent apoptosis. Caspase-2 (Casp2; Nedd-2, Ich-1) is a developmentally regulated initiator caspase, which poorly cleaves other caspases but can initiate mitochondrial outer membrane permeabilization.

Zhao et al. nature medicine advance online publication (Impact Factor 58.7)

In Alzheimer’s disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines.(...)

Kim et al. Cell 175, 133–145, September 20, 2018 (Impact Factor 45.5)

In Alzheimer’s disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines.(...)

Kim et al. Cell Metabolism 34, 1–13, October 4, 2022 ª 2022 Elsevier Inc (Impact Factor 27.7)

Kim et al. show that while diets rich in glucose lead to insulin-dependent SREBP activation via the SCAP pathway, diets rich in the saturated fatty acids (FAs) and fructose trigger ER stress and INSIG2 induction, which inhibits SCAP-dependent SREBP activation. Instead, ER stress results in Casp2/PIDDosome dependent SREBP activation (...)