New insight into transglutaminase 2 and link to neurodegenerative diseases.

Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affects the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins.

Isocitrate protects DJ-1 null dopaminergic cells from oxidative stress through NADP+-dependent isocitrate dehydrogenase (IDH).

DJ-1 is one of the causative genes for early onset familiar Parkinson's disease (PD) and is also considered to influence the pathogenesis of sporadic PD. DJ-1 has various physiological functions which converge on controlling intracellular reactive oxygen species (ROS) levels. In RNA-sequencing analyses searching for novel anti-oxidant genes downstream of DJ-1, a gene encoding NADP+-dependent isocitrate dehydrogenase (IDH), which converts isocitrate into α-ketoglutarate, was detected.

Multiple teeth fractures in dentinogenesis imperfecta: a case report.

Dentinogenesis imperfecta (DGI) is a hereditary defect consisting of opalescent teeth composed of irregularly formed and hypomineralized dentin. This paper presents the multiple fractures of DGI-affected teeth and suggests the reason of low fracture resistance by observing the dentin microstructures directly using scanning electron microscope (SEM) and by measuring its surface hardness using the Vickers hardness test. SEM revealed that while the enamel microstructure was similar in the DGI-affected and normal teeth, the microstructure of the DGI-affected dentin was poorly woven and more loosely packed than that of the normal dentin.

PINK1 phosphorylates transglutaminase 2 and blocks its proteasomal degradation.

Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal loss and the formation of abnormal protein aggregates, referred to as Lewy bodies (LBs). PINK1 is a serine/threonine protein kinase that protects cells from stress-induced mitochondrial dysfunction. PINK1 gene mutations cause one form of autosomal recessive early-onset PD.

Osteoconduction capacity of human deciduous and permanent teeth ash in a rat calvarial bone defect model.

The aim of this study was to confirm the osteoconduction capacities and determine the potential of permanent teeth ash (PTA), and deciduous teeth ash (DTA) as bone substitutes. Rats (n = 71) were divided randomly into four groups: sham, micro macroporous biphasic calcium phosphate (MBCP), PTA, and DTA. A sample of the each group was transplanted into preformed 8-mm calvarial defects (one per rat).

Covalent NEDD8 conjugation increases RCAN1 protein stability and potentiates its inhibitory action on calcineurin.

Similar to ubiquitin, regulatory roles for NEDD8 (neural precursor cell-expressed developmentally down-regulated 8) are being clarified during cell growth, signal transduction, immune response, and development. However, NEDD8 targets and their functional alterations are not well known. Regulator of calcineurin 1 (RCAN1/DSCR1P1) is located near the Down syndrome critical region on the distal part of chromosome 21, and its gene product is an endogenous inhibitor of calcineurin signaling.

Identification of RUNX3 as a component of the MST/Hpo signaling pathway.

Recent genetic screens of fly mutants and molecular analysis have revealed that the Hippo (Hpo) pathway controls both cell proliferation and cell death. Deregulation of its human counterpart (the MST pathway) has been implicated in human cancers. However, how this pathway is linked with the known tumor suppressor network remains to be established.

ASK1 negatively regulates the 26 S proteasome.

The 26 S proteasome, composed of the 20 S core and 19 S regulatory particle, plays a central role in ubiquitin-dependent proteolysis. Disruption of this process contributes to the pathogenesis of the various diseases; however, the mechanisms underlying the regulation of 26 S proteasome activity remain elusive. Here, cell culture experiments and in vitro assays demonstrated that apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase family, negatively regulated 26 S proteasome activity.

Parkin directly modulates 26S proteasome activity.

Parkinson's disease (PD) is a common neurodegenerative disease that involves the deterioration of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD remains poorly understood, recent genetic, postmortem, and experimental evidence shows that abnormal protein accumulation and subsequent aggregate formation are prominent features of both sporadic and familial PD. While proteasome dysfunction is observed in PD, diverse mutations in the parkin gene are linked to early-onset autosomal-recessive forms of familial PD.