Sodium fusidate prevents protein aggregation of silk fibroin and offers new perspectives for human lens material disaggregation

A native chemical chaperone in the human eye lens

10.1101/2020.12.16.423154 ◽

2020 ◽

Author(s):

Eugene Serebryany ◽

Sourav Chowdhury ◽

Christopher N. Woods ◽

David C. Thorn ◽

Nicki E Watson ◽

...

Keyword(s):

Protein Aggregation ◽

Vision Loss ◽

Human Lens ◽

Lens Crystallins ◽

Chemical Chaperone ◽

Negative Stain ◽

Molecular Mechanism Of Action ◽

Redox Buffers ◽

Rate Limiting

Cataract is one of the most prevalent protein aggregation disorders and still the most common cause of vision loss worldwide. The metabolically quiescent core region of the human lens lacks cellular or protein turnover; it has therefore evolved remarkable mechanisms to resist light-scattering protein aggregation for a lifetime. We now report that one such mechanism involves an unusually abundant lens metabolite, myo-inositol, suppressing aggregation of lens crystallins. We quantified aggregation suppression using our previously well-characterized in vitro aggregation assays of oxidation-mimicking human γD-crystallin variants and investigated myo-inositol's molecular mechanism of action using solution NMR, negative-stain TEM, differential scanning fluorometry, thermal scanning Raman spectroscopy, turbidimetry in redox buffers, and free thiol quantitation. Unlike many known chemical chaperones, myo-inositol's primary target was neither the native nor the unfolded state of the protein, nor the final aggregated state, but rather the rate-limiting bimolecular step on the aggregation pathway. Given recent metabolomic evidence that it is severely depleted in human cataractous lenses compared to age-matched controls, we suggest that maintaining or restoring healthy levels of myo-inositol in the lens may be a simple, safe, and globally accessible strategy to prevent or delay lens opacification due to age-onset cataract.

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An Ultra-Structural Study of Human Melanoma in Vivo and Vitro

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100091275 ◽

1976 ◽

Vol 34 ◽

pp. 258-259

Author(s):

James R. Gaylor ◽

Fredda Schafer ◽

Robert E. Nordquist

Keyword(s):

Endoplasmic Reticulum ◽

Golgi Apparatus ◽

Protein Aggregation ◽

Structural Study ◽

Human Melanoma ◽

Protein Matrix ◽

Early Form ◽

Endoplasmic Reticulum Protein ◽

Mitochondrial Origin

Several theories on the origin of the melanosome exist. These include the Golgi origin theory, in which a tyrosinase-rich protein is "packaged" by the Golgi apparatus, thus forming the early form of the melanosome. A second theory postulates a mitochondrial origin of melanosomes. Its author contends that the melanosome is a modified mitochondria which acquires melanin during its development. A third theory states that a pre-melanosome is formed in the smooth or rough endoplasmic reticulum. Protein aggregation is suggested by one author as a possible source of the melanosome. This fourth theory postulates that the melanosome originates when the protein products of several genetic loci aggregate in the cytoplasm of the melanocyte. It is this protein matrix on which the melanin is deposited. It was with these theories in mind that this project was undertaken.

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A novel P159L mutation in the Parkin gene related to autosomal dominantly inherited late onset parkinsonism and protein aggregation

Aktuelle Neurologie ◽

10.1055/s-2004-832982 ◽

2004 ◽

Vol 31 (S 1) ◽

Author(s):

R Krüger ◽

FP Marx ◽

D Berg ◽

C Holzmann ◽

T Müller ◽

...

Keyword(s):

Protein Aggregation ◽

Late Onset ◽

Parkin Gene

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Increased glycosylation of human lens epithelial basement membrane in diabetes mellitus

Korean Journal of Ophthalmology ◽

10.3341/kjo.1994.8.1.26 ◽

1994 ◽

Vol 8 (1) ◽

pp. 26 ◽

Cited By ~ 1

Author(s):

Dong H. Shin ◽

Shlomo S. Mandel ◽

Jin H. Lee ◽

Brett Ernst ◽

Bruce L. Newman ◽

...

Keyword(s):

Diabetes Mellitus ◽

Basement Membrane ◽

Human Lens ◽

Epithelial Basement Membrane ◽

Epithelial Basement

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Optimum Infinite is a new era of oxygen permeability material for contact lenses

The Eye ◽

10.33791/2222-4408-2020-1-44-46 ◽

2020 ◽

Vol 22 (129) ◽

pp. 44-46

Author(s):

Mark Eddleston

Keyword(s):

Contact Lens ◽

Oxygen Permeability ◽

Contact Lenses ◽

New Era ◽

Lens Material ◽

Insight Into

Optimum Infinite is a new GP contact lens material, with an oxygen permeability of 180 barrer and was launched by Contamac at the GSLS 2019. This article provides an insight into the development and characteristics of this breakthrough material.

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