Impairment of the ubiquitin proteasome system (UPS) has been proposed to play an important role in the pathogenesis of Parkinson's disease (PD). Mice with UPS impairment in the nigra have been used for investigating mechanisms underlying neurodegeneration and for testing pre-clinical drugs to treat PD. However, the pathological, biochemical and behavioral features of UPS impairment animal model...

SARM1 is a key regulator of axonal degeneration. However, SARM1 mechanism of action is not clear. In this issue of Neuron, Essuman et al. (2017) reveal an intrinsic NADase activity in the SARM1-TIR domain that is required for axonal degeneration.

The role of microtubule (MT) dysfunction in Parkinson's disease is emerging. It is still unknown whether it is a cause or a consequence of neurodegeneration. Our objective was to assess whether alterations of MT stability precede or follow axonal transport impairment and neurite degeneration in experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl mic...

SOD1 is a cause of the fatal, paralytic disorder ALS. Although mechanisms underlying mutant SOD1 neurotoxicity remain uncertain, this protein associates with mitochondria. In this issue of Neuron, Israelson et al. show that mutant SOD1 binds and inhibits the mitochondrial channel VDAC1. This finding sheds light onto possible molecular links between mutant SOD1, mitochondrial dysfunction, and sp...

The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acryl...

The G59S missense mutation at the conserved microtubule-binding domain of p150 , a major component of dynein/dynactin complex, has been linked to an autosomal dominant form of motor neuron disease (MND). To study how this mutation affects the function of the dynein/dynactin complex and contributes to motor neuron degeneration, we generated p150 glued G59S knock-in mice. We found that the G59S m...

Spinal muscular atrophy (SMA) is caused by deletion or specific mutations of the telomeric survival motor neuron ( SMN ) gene on human chromosome 5. The human SMN gene, in contrast to the Smn gene in mouse, is duplicated and the centromeric copy on chromosome 5 codes for transcripts which preferentially lead to C-terminally truncated SMN protein. Here we show that a 46% reduction of Smn protein...

Altered gene transcription has been implicated in the pathogenesis of polyglutamine-dependent neurodegeneration. In this issue of Neuron, Sopher et al. demonstrate that androgen receptors containing expanded polyglutamine cause decreased expression of vascular endothelial growth factor (VEGF) by interfering with cAMP response element binding protein binding protein (CBP), thereby contributing t...

  Background and Objectives: Studies have documented the morhplogical, neurochemical and functional difference between the dorsal and ventral zones of hippocampus. The aim of this study was to assess the effects of chronic diabetes mellitus type1 on ventral and dorsal zones of hippocampus. Methods: Experimental diabetes was induced by stereptozotocin at a dose of 60 mg/kg. At the end of 8 wee...

The recent investigation suggested that the TDP-43 protein was closely related to the motor neuron degeneration in amyotrophic lateral sclerosis (ALS), but the pathogenesis contributed to motor neuron degeneration largely remained unknown. Therefore, we detected the alteration of TDP-43 expression and distribution in the adult spinal cord of the SOD1 G93A transgenic mouse model for searching th...