One of the most significant problems facing developmental biologists who do not work on an organism with well-developed genetics - and even for some who do - is how to inhibit the action of a gene of interest during development so as to learn about its normal biological function. A widely adopted approach is to use antisense technologies, and especially morpholino antisense oligonucleotides. In this article, we review the use of such reagents and present examples of how they have provided insights into developmental mechanisms. We also discuss how the use of morpholinos can lead to misleading results, including off-target effects, and we suggest controls that will allow researchers to interpret morpholino experiments correctly.

/pdf/controlling-morpholino-experiments-don-t-stop-making-3kenki0cwz.pdf

Controlling morpholino experiments: don't stop making antisense

Parkinson’s disease (PD) coincides with a dramatic loss of dopaminergic neurons within the substantia nigra. A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates reactive oxygen species (ROS) and DA oxidation can lead to endogenous neurotoxins whereas some DA derivatives show antioxidative effects. Therefore, DA metabolism is of special importance for neuronal redox-homeostasis and viability. In this review we highlight different aspects of dopamine metabolism in the context of PD and neurodegeneration. Since most reviews focus only on single aspects of the DA system, we will give a broader overview by looking at DA biosynthesis, sequestration, degradation and oxidation chemistry at the metabolic level, as well as at the transcriptional, translational and posttranslational regulation of all enzymes involved. This is followed by a short overview of cellular models currently used in PD research. Finally, we will address the topic from a medical point of view which directly aims to encounter PD.

/pdf/complexity-of-dopamine-metabolism-kgg8jy8ri3.pdf

Complexity of dopamine metabolism

For the past 10 years, the annual ‘Antibodies to watch’ articles have provided updates on key events in the late-stage development of antibody therapeutics, such as first regulatory review or appro...

https://tandfonline.com/doi/pdf/10.1080/19420862.2018.1556465

Antibodies to watch in 2019.

Forty-five years ago, Roger Sperry, Joseph Bogen and I embarked on what are now known as the modern split-brain studies. These experiments opened up new frontiers in brain research and gave rise to much of what we know about hemispheric specialization and integration. The latest developments in split-brain research build on the groundwork laid by those early studies. Split-brain methodology, on its own and in conjunction with neuroimaging, has yielded insights into the remarkable regional specificity of the corpus callosum as well as into the integrative role of the callosum in the perception of causality and in our perception of an integrated sense of self.

Forty-five years of split-brain research and still going strong.

Alzheimer’s disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.

/pdf/autophagy-and-alzheimer-s-disease-from-molecular-mechanisms-25ghgdajkr.pdf

Natarajan

Papers

The Nobel Prize in physiology or medicine