How Do Lipids Localize in Lewy Bodies?

Lewy bodies are the pathological hallmark of Parkinson's disease (PD). While fibrillar α-synuclein (αS) is the main protein component of Lewy bodies, these structures also contain lipids. To elucidate the presence of lipids in Lewy bodies, we investigated the interaction of lipids with monomeric and fibrillar αS. In vitro, lipid membranes accelerated αS fibril formation under physiological conditions. Moreover lipids and small vesicles co-localized with supra-fibrillar structures and individual αS fibrils suggesting that aggregation initiates at the membrane. The presence of lipids in Lewy bodies may therefore be an indication that cell membranes are the major target in aggregation induced neuronal cell deat

How important is the N-terminal acetylation of alpha-synuclein for its function and aggregation into amyloids?

N-α-acetylation is a frequently occurring post-translational modification in eukaryotic proteins. It has manifold physiological consequences on the regulation and function of several proteins, with emerging studies suggesting that it is a global regulator of stress responses. For decades, in vitro biochemical investigations into the precise role of the intrinsically disordered protein alpha-synuclein (αS) in the etiology of Parkinson’s disease (PD) were performed using non-acetylated αS. The N-terminus of α-synuclein is now unequivocally known to be acetylated in vivo, however, there are many aspects of this post-translational modifications that are not understood well. Is N-α-acetylation of αS a constitutive modification akin to most cellular proteins, or is it spatio-temporally regulated? Is N-α-acetylation of αS relevant to the as yet elusive function of αS? How does the N-α-acetylation of αS influence the aggregation of αS into amyloids? Here, we provide an overview of the current knowledge and discuss prevailing hypotheses on the impact of N-α-acetylation of αS on its conformational, oligomeric, and fibrillar states. The extent to which N-α-acetylation of αS is vital for its function, membrane binding, and aggregation into amyloids is also explored here. We further discuss the overall significance of N-α-acetylation of αS for its functional and pathogenic implications in Lewy body formation and synucleinopathies

Splanchnic Nerve Block as a Bridge Therapy in Painful Chronic Pancreatitis During COVID 19 Pandemic: A Case Report

Agonizing and debilitating pain is what most patients with chronic pancreatitis endure. Chronic pain often leads to depression and poor quality of life. Surgical decompression can result in permanent pain relief by reducing intraductal hypertension. Elective surgical procedures had to be postponed during the times of the Covid-19 pandemic as the resources including oxygen supplies, workforce, and ventilators were dedicated to the service of Covid-19 patients. We present a case of 20 year-old-male suffering from severe abdominal pain due to chronic pancreatitis refractory to analgesic medications. In view of the refractory pain and inability to proceed with surgery due to the pandemic, we subjected him to undergo splanchnic nerve block (SNB) with local anesthetic and steroid.  SNB provided adequate analgesia and enabled the patient to tide over the crisis. To our knowledge, no case has been reported using a combination of local anesthetic and steroid in SNB for a patient with chronic pancreatitis

Entropy of water and the temperature-induced stiffening of amyloid networks

In water, networks of semi-flexible fibrils of the protein $\alpha$-synuclein stiffen significantly with increasing temperature. We make plausible that this reversible stiffening is a result of hydrophobic contacts between the fibrils that become more prominent with increasing temperature. The good agreement of our experimentally observed temperature dependence of the storage modulus of the network with a scaling theory linking network elasticity with reversible crosslinking enables us to quantify the endothermic binding enthalpy and an estimate the effective size of hydrophobic patches on the fibril surface.Comment: 13 pages, 6 figure

Modeling and experimental verification of the dynamic interaction of an AFM-tip with a photonic crystal microcavity

We present a transmission model for estimating the effect of the atomic-force microscopy tapping tip height on a photonic crystal microcavity (MC). This model uses a fit of the measured tip-height-dependent transmission above a “hot spot” in the MC. The predicted transmission versus average tapping height is in good agreement with the values obtained from tapping mode experiments. Furthermore, we show that for the existing, nonoptimized structure, the transmission coefficient can be tuned between 0.32 and 0.8 by varying the average tapping height from 26 to 265 nm. A transmission larger than that of the undisturbed cavity at resonance was observed at specific tip locations just outside the cavity-terminating holes