Background-Recent studies indicate an increased frequency of mutations in the gene for Gaucher disease, glucocerebrosidase (GBA), among patients with Parkinson disease. An international collaborative study was conducted to ascertain the frequency of GBA mutations in ethnically diverse patients with Parkinson disease.

Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Although the mutant protein is widely expressed, the earliest and most striking neuropathological changes are observed in the striatum. Here we show dramatic mutation length increases (gains of up to 1000 CAG repeats) in human striatal cells early in the disease course, most likely before the onset of pathological cell loss. Studies of knock-in HD mouse models indicate that the size of the initial CAG repeat mutation may influence both onset and tissue-specific patterns of age-dependent, expansion-biased mutation length variability. Given that CAG repeat length strongly correlates with clinical severity, we suggest that somatic increases of mutation length may play a major role in the progressive nature and cell-selective aspects of both adult-onset and juvenile-onset HD pathogenesis and we discuss the implications of this interpretation of the data presented.

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Parkinson’s disease (PD) is caused by progressive neurodegeneration of dopaminergic (DAergic) neurons with abnormal accumulation of α-synuclein in substantia nigra (SN). Studies have suggested the potential involvement of dopamine, iron, calcium, mitochondria and neuroinflammation in contributing to overwhelmed oxidative stress and neurodegeneration in PD. Function studies on PD-causative mutations of SNCA, PRKN, PINK1, DJ-1, LRRK2, FBXO7 and ATP13A2 further indicate the role of oxidative stress in the pathogenesis of PD. Therefore, it is reasonable that molecules involved in oxidative stress, such as DJ-1, coenzyme Q10, uric acid, 8-hydroxy-2’-deoxyguanosin, homocysteine, retinoic acid/carotenes, vitamin E, glutathione peroxidase, superoxide dismutase, xanthine oxidase and products of lipid peroxidation, could be candidate biomarkers for PD. Applications of antioxidants to modulate oxidative stress could be a strategy in treating PD. Although a number of antioxidants, such as creatine, vitamin E, coenzyme Q10, pioglitazone, melatonin and desferrioxamine, have been tested in clinical trials, none of them have demonstrated conclusive evidence to ameliorate the neurodegeneration in PD patients. Difficulties in clinical studies may be caused by the long-standing progression of neurodegeneration, lack of biomarkers for premotor stage of PD and inadequate drug delivery across blood–brain barrier. Solutions for these challenges will be warranted for future studies with novel antioxidative treatment in PD patients.