Hirnelektrische und elektromyographische Untersuchungen beim Migr�nesyndrom

Becher, Fritz

doi:10.1007/bf00249433

Cited by 4 publications

(1 citation statement)

References 3 publications

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“…Later studies on GLP-1 at other pH values and on a C-terminally amidated form of GLP-1 showed that net charge is likely a factor in determining whether off-pathway species are formed. 29 In addition, more recent studies have shown that the stable, off-pathway oligomer formed under some conditions can inhibit aggregation. 26 What is lacking in these studies is an understanding of how pH changes the structural ensemble of GLP-1, thus facilitating the population of either on- or off-pathway oligomers.…”

Section: Introductionmentioning

confidence: 99%

Energy Landscapes and Structural Ensembles of Glucagon-like Peptide-1 Monomers

Keith,

Brichtová,

Barber

et al. 2024

J. Phys. Chem. B

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While GLP-1 and its analogues are important pharmaceutical agents in the treatment of type 2 diabetes and obesity, their susceptibility to aggregate into amyloid fibrils poses a significant safety issue. Many factors may contribute to the aggregation propensity, including pH. While it is known that the monomeric structure of GLP-1 has a strong impact on primary nucleation, probing its diverse structural ensemble is challenging. Here, we investigated the monomer structural ensembles at pH 3, 4, and 7.5 using state-of-the-art computational methods in combination with experimental data. We found significant stabilization of β-strand structures and destabilization of helical structures at lower pH, correlating with observed aggregation lag times, which are lower under these conditions. We further identified helical defects at pH 4, which led to the fastest observed aggregation, in agreement with our far-UV circular dichroism data. The detailed atomistic structures that result from the computational studies help to rationalize the experimental results on the aggregation propensity of GLP-1. This work provides a new insight into the pH-dependence of monomeric structural ensembles of GLP-1 and connects them to experimental observations.

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Section: Introductionmentioning

confidence: 99%

Energy Landscapes and Structural Ensembles of Glucagon-like Peptide-1 Monomers

Keith,

Brichtová,

Barber

et al. 2024

J. Phys. Chem. B

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Elektrencephalographische Befunde bei Migr�ne

Krischek

1956

Deutsche Zeitschrift f. Nervenheilkunde

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Grenzen und Möglichkeiten neurophysiologischer Methoden in der Erforschung und Diagnostik der Migräne

Thoden

Wichert

1991

Schmerz

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In parallel with the development of the various electrophysiological methods now available, the clinical syndrome of migraine has been repeatedly analyzed with the aid of these tools, in attempts to track its course with reference to electrophysiological parameters. A survey of the international literature reveals the following EEG findings. (1) In patients with different forms of headache without structural lesions the distribution of normal and abnormal EEG recordings during headachefree intervals resembles that seen among healthy subjects. (2) In common migraine, nonfocal and nonspecific abnormalities are reflected in up to 65% of all EEG recordings during the migraine-free interval. (3) Focal EEG abnormalities during a migraine attack are relatively rare, generally occurring only during migraines with transient focal neurological disturbances. (4) It is very rare for there to be permanent focal changes that are apparent during both pain-free intervals and migraine attacks. In the presence of such changes very careful diagnosis is necessary to exclude symptomatic lesions. (5) In up to 53% of migraineurs a few minutes' hyperventilation leads to generalized slow, wide-amplitude, sometimes episodic waves in the EEG. Similar changes also occur in healthy subjects, but are less common, less intense and of shorter duration. (6) There is a statistically significant correlation between the occurrence of a migraine and EEG activation by photic stimulation at frequencies over 20 Hz. (7) No unequivocal results obtained in large series of patients with train mapping are yet available.

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Hirnelektrische und elektromyographische Untersuchungen beim Migr�nesyndrom

Cited by 4 publications

References 3 publications

Energy Landscapes and Structural Ensembles of Glucagon-like Peptide-1 Monomers

Energy Landscapes and Structural Ensembles of Glucagon-like Peptide-1 Monomers

Elektrencephalographische Befunde bei Migr�ne

Grenzen und Möglichkeiten neurophysiologischer Methoden in der Erforschung und Diagnostik der Migräne

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