Peptoids: Emerging Therapeutics for Neurodegeneration
Lauren M. Wolf,1 Shannon L. Servoss,2 and Melissa A. Moss1,3,*
In recent decades, the increasing prevalence of age-associated neurodegenerative diseases has underscored the need for targeted therapeutic strategies and novel diagnostics. Peptide-based neurotherapeutics offer high specificity and tolerability but are limited by proteolytic degradation in vivo. Peptoids, or N-substituted glycines, are versatile peptidomimetics that evade proteolytic degradation yet maintain many qualities that render peptides attractive neurotherapeutic candidates. These molecules may be engineered to their application through modifications that enhance structural stability and reactivity and can withstand various physiological stressors to retain their intended function within anomalous microenvironments.
Peptoids generally demonstrate greater cellular permeability than their corresponding peptides, are less immunogenic, and can be administered intranasally, all properties that enhance their potential as neurotherapeutics. Peptoids have primarily been explored as aggregation inhibitors to prevent the deleterious protein plaque deposition associated with several neurodegenerative disorders. However, novel research has uncovered the potential of peptoids toward additional neurotherapeutic applications. Peptoids can modulate cell signaling pathways involved in axonal function and current modulation and can block cell signaling events associated with apoptosis. In addition, these peptidomimetics are able to function as anti- inflammatory agents via multiple mechanisms. Moreover, the versatility and low cost of peptoids render them ideal instruments in biomarker detection, discovery, and imaging. This mini-review explores these diverse applications of peptoids within the context of neurodegenerative disease.
DOI: 10.29245/2572.942X/2017/7.1135 View / Download Pdf New psychotherapeutic approaches in adult ADHD - acknowledging biographical factors
Caroline Lücke1*, Alexandra P. Lam1, Helge H. O. Muller1, Alexandra Philipsen1,2
Cognitive behavioral therapy (CBT) is the standard form of psychotherapy currently used in adult attention deficit hyperactivity disorder (ADHD). However, biographical factors, such as chronic negative feedback in childhood, which may likely play a role in ADHD as a developmental disorder, are usually not substantially addressed by CBT. In recent years, schema therapy has received increasing attention as an effective therapy approach for chronic psychiatric disorders. A core feature of schema therapy is the identification and targeting of early maladaptive schemas, which are dysfunctional patterns and beliefs resulting from childhood experiences. Recently, two studies have demonstrated an increased prevalence of maladaptive schemas in adult ADHD. Thus, schema therapy might constitute a potentially promising approach in the treatment of ADHD, especially with regard to secondary problems such as poor coping strategies or impaired self-perception. However, randomized controlled clinical studies are needed to support that theory. Here, we provide an overview on the topic of biography-oriented therapy approaches in relation to adult ADHD, summarize current literature and discuss implications for future research.
DOI: 10.29245/2572.942X/2017/7.1138 View / Download Pdf Recent advances in modelling of cerebellar ataxia using induced pluripotent stem cells
Maggie M. K. Wong1, Lauren M. Watson1 and Esther B. E. Becker1
The cerebellar ataxias are a group of incurable brain disorders that are caused primarily by the progressive dysfunction and degeneration of cerebellar Purkinje cells. The lack of reliable disease models for the heterogeneous ataxias has hindered the understanding of the underlying pathogenic mechanisms as well as the development of effective therapies for these devastating diseases. Recent advances in the field of induced pluripotent stem cell (iPSC) technology offer new possibilities to better understand and potentially reverse disease pathology. Given the neurodevelopmental phenotypes observed in several types of ataxias, iPSC-based models have the potential to provide significant insights into disease progression, as well as opportunities for the development of early intervention therapies. To date, however, very few studies have successfully used iPSC-derived cells to cerebellar ataxias. In this review, we focus on recent breakthroughs in generating human iPSC-derived Purkinje cells. We also highlight the future challenges that will need to be addressed in order to fully exploit these models for the modelling of the molecular mechanisms underlying cerebellar ataxias and the development of effective therapeutics.
DOI: 10.29245/2572.942X/2017/7.1134 View / Download Pdf What can be learned from white matter alterations in antisocial girls.
Willeke M. Menks1, Christina Stadler1 and Nora M. Raschle1
Antisocial behavior in youths constitutes a major public health problem worldwide. Conduct disorder is a severe variant of antisocial behavior with higher prevalence rates for boys (12%) as opposed to girls (7%). A better understanding of the underlying neurobiological mechanisms of conduct disorder is warranted to improve identification, diagnosis, or treatment. Functional and structural neuroimaging studies have indicated several key brain regions within the limbic system and prefrontal cortex that are altered in youths with conduct disorder. Examining the structural connectivity, i.e. white matter fiber tracts connecting these brain areas, may further inform about the underlying neural mechanisms. Diffusion tensor imaging (DTI) is a non-invasive technique that can evaluate the white matter integrity of fiber tracts throughout the brain. To date, DTI studies have found several white matter tracts that are altered in youths with conduct disorder. However, a majority of these studies have focused on male or mixed-gender groups, and only a few studies have specifically investigated white matter alterations in girls with conduct disorder. Ultimately, studies that directly compare boys and girls with conduct disorder are necessary to identify possible sexual dimorphic neural alterations and developmental trajectories of conduct disorder in youths.
DOI: 10.29245/2572.942X/2017/7.1139 View / Download Pdf