NMDA antagonists as Parkinson's disease therapy: disseminating the evidence

Förskolans fysiska inomhusmiljö ska vara stimulerande och locka barnen till lek och lärande, och det kräver av förskollärare att de ständigt reflekterar över och bearbetar den som en del av sitt arbete. Studiens syfte är att få fördjupad kunskap om förskolans fysiska inomhusmiljö som ett verktyg för lärande. Den baseras på förskollärares inställning och erfarenheter och därför används kvalitativa intervjuer som datainsamlingsmetod. Fem förskollärare från tre olika förskolor intervjuades. Förskollärarna såg många möjligheter med den fysiska miljöns bidrag till lärande, men det kommer fram att det även finns många svårigheter. De strävar efter att miljön ska anpassas efter varje barns behov och intresse, och att allt ska vara tillgängligt för barnen. De känner sig emellertid begränsade av stora barngrupper, trånga lokaler och ett behov av att skydda de yngre barnen från saker som kan fastna i halsen. Att försöka förstå många barns intentioner samtidigt är en viktig uppgift i förskolearbete. Förskollärare uppvisar även olika barnsyner i sina berättelser om den fysiska inomhusmiljöns utformning

Genetic and molecular aspects of spinocerebellar ataxias

The group of spinocerebellar ataxias (SCAs) includes more than 20 subgroups based only on genetic research. The “ataxia genes” are autosomal; the “disease-alleles” are dominant, and many of them, but not all, encode a protein with an abnormally long polyglutamine domain. In DNA, this domain can be detected as an elongated CAG repeat region, which is the basis of genetic diagnostics. The polyglutamine tails often tend to aggregate and form inclusions. In some cases, protein–protein interactions are the key to understanding the disease. Protein partners of ataxia proteins include phosphatases and components of chromatin and the transcriptional machinery. To date, investigation of spinocerebellar ataxias involves population genetics, molecular methods, and studying model organisms. However, there is still no efficient therapy for patients. Here, we review the genetic and molecular data gained on spinocerebellar ataxias

Clinical characteristics and possible drug targets in autosomal dominant spinocerebellar ataxias

The autosomal dominant spinocerebellar ataxias (SCAs) belong to a large and expanding group of neurodegenerative disorders. SCAs comprise more than 40 subtypes characterized by progressive ataxia as a common feature. The most prevalent diseases among SCAs are caused by CAG repeat expansions in the coding-region of the causative gene resulting in polyglutamine (polyQ) tract formation in the encoded protein. Unfortunately, there is no approved therapy to treat cerebellar motor dysfunction in SCA patients. In recent years, several studies have been conducted to recognize the clinical and pathophysiological aspects of the polyQ SCAs more accurately. This scientific progress has provided new opportunities to develop promising gene therapies, including RNA interference and antisense oligonucleotides.The aim of the current work is to give a brief summary of the clinical features of SCAs and to review the cardinal points of pathomechanisms of the most common polyQ SCAs. In addition, we review the last few years promising gene suppression therapies of the most frequent polyQ SCAs in animal models, on the basis of which human trials may be initiated in the near future

Tryptophan 2,3-dioxygenase, a novel therapeutic target for Parkinson's disease

Alterations in the activity of tryptophan 2,3-dioxygenase (TDO) cause imbalances in the levels of serotonin and other neuroactive metabolites which can contribute to motor, psychiatric, gastrointestinal, and other dysfunctions often seen in Parkinson's disease (PD). TDO is a key enzyme of tryptophan metabolism at the entry of the kynurenine pathway (KP) which moderates production of neuroactive compounds primarily outside the central nervous system (CNS). Recent data from experimental models indicate that TDO modulation could have beneficial effects on PD symptoms not targeted by traditional dopamine substitution therapies.Areas covered: Based on data available in PubMed and ClinicalTrials databases up until 1st August 2021, we summarize current knowledge of KP alterations in relation to PD. We overview effects of TDO inhibition in preclinical models of neurodegeneration and discuss findings of the impact of enzyme inhibition on motor, memory and gastrointestinal dysfunctions and neuronal cell loss.Expert opinion: TDO inhibition potentially alleviates motor and non-motor dysfunctions of PD. However, data suggesting harmful effects of long term TDO inhibition raise concerns. To exploit possibilities of TDO inhibitory treatment, development of further selective TDO inhibitor compounds with good bioavailability features and models adequately replicating PD symptoms of systemic origin should be prioritized