👤 Roberta Cascella

BackgroundHigh intensity interval training (HIIT) involves vigorous intensity exercise bouts interspersed with low intensity bouts. Despite growing interest, the optimal dosage and clinical adaptability of HIIT in Parkinson's disease (PD) remain unclear. This scoping review synthesized the literature on systemic adaptations underlying HIIT in PD and developed a clinical framework while considering chronotropic incompetence, orthostatic hypotension, and disease progression.MethodsThree databases were searched for studies that incorporated HIIT interventions in PD. The Template for Intervention Description and Replication checklist was used to characterize the quality of intervention reporting.ResultsA total of 285 studies were screened, of which 10 studies were included. HIIT was administered 2-3 times/week for 30-60 min/session over 8-12 weeks. Seven studies used moderate-volume HIIT and three studies used high-volume HIIT protocols. The quality of intervention reporting was fair to good. HIIT improved cardiorespiratory fitness, motor severity, and functional mobility in PD, however, improvements were comparable to moderate intensity continuous training (MICT). HIIT may facilitate neuroplasticity by increasing brain-derived neurotrophic factor levels and dopamine transporter uptake. We recommend that HIIT programs for individuals with autonomic dysfunction use individualized heart rate targets, and perceived exertion for determining exercise intensity, and incorporate longer duration programs (>12 weeks).ConclusionHIIT is a well-tolerated intervention that may improve cardiorespiratory fitness, disease severity, and certain neurobiological markers in mild-moderate PD, with benefits similar to MICT. Larger trials comparing different HIIT volumes are needed to identify optimal exercise volume to inform individualized exercise prescription. Show less

High cholesterol levels are a risk factor for the development of Alzheimer's disease. Experiments investigating the influence of cholesterol on the proteolytic processing of the amyloid precursor protein (APP) by the β-secretase Bace1 and on their proximity in cells have led to conflicting results. By using a fluorescence bioassay coupled with flow cytometry we found a direct correlation between the increase in membrane cholesterol amount and the degree of APP shedding in living human neuroblastoma cells. Analogue results were obtained for cells overexpressing an APP mutant that cannot be processed by α-secretase, highlighting the major influence of cholesterol enrichment on the cleavage of APP carried out by Bace1. By contrast, the cholesterol content was not correlated with changes in membrane dynamics of APP and Bace1 analyzed with single molecule tracking, indicating that the effect of cholesterol enrichment on APP processing by Bace1 is uncoupled from changes in their lateral diffusion. Show less

A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ). To show that pericentriolar material 1 protein (PCM1) forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a crucial pathway for cortical development associated with the pathology of SZ. To identify mutations in the PCM1 gene in an SZ population. Interaction of DISC1, PCM1, and BBS proteins was assessed by immunofluorescent staining and coimmunoprecipitation. Effects of PCM1, DISC1, and BBS on centrosomal functions and corticogenesis in vivo were tested by RNA interference. The PCM1 gene was examined by sequencing 39 exons and flanking splice sites. Probands and controls were from the collection of one of us (A.E.P.). Thirty-two probands with SZ from families that had excess allele sharing among affected individuals at 8p22 and 219 white controls. Protein interaction and recruitment at the centrosome in cells; neuronal migration in the cerebral cortex; and variant discovery in PCM1 in patients with SZ. PCM1 forms a complex with DISC1 and BBS4 through discrete binding domains in each protein. DISC1 and BBS4 are required for targeting PCM1 and other cargo proteins, such as ninein, to the centrosome in a synergistic manner. In the developing cerebral cortex, suppression of PCM1 leads to neuronal migration defects, which are phenocopied by the suppression of either DISC1 or BBS4 and are exacerbated by the concomitant suppression of both. Furthermore, a nonsense mutation that segregates with SZ spectrum psychosis was found in 1 family. Our data further support for the role of centrosomal proteins in cortical development and suggest that perturbation of centrosomal function contributes to the development of mental diseases, including SZ. Show less