scholarly journals PINK1 signalling in neurodegenerative disease

2021 ◽  
Author(s):  
Daniel R. Whiten ◽  
Dezerae Cox ◽  
Carolyn M. Sue
Keyword(s):  
Neurodegenerative Disease ◽  
Mitochondrial Membrane ◽  
Full Length ◽  
Cellular Survival ◽  
Cell Dysfunction ◽  
Neuronal Protein ◽  
Survival Signal ◽  
Human Pathology ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Abstract PTEN-induced kinase 1 (PINK1) impacts cell health and human pathology through diverse pathways. The strict processing of full-length PINK1 on the outer mitochondrial membrane populates a cytoplasmic pool of cleaved PINK1 (cPINK1) that is constitutively degraded. However, despite rapid proteasomal clearance, cPINK1 still appears to exert quality control influence over the neuronal protein homeostasis network, including protein synthesis and degradation machineries. The cytoplasmic concentration and activity of this molecule is therefore a powerful sensor that coordinates aspects of mitochondrial and cellular health. In addition, full-length PINK1 is retained on the mitochondrial membrane following depolarisation, where it is a powerful inducer of multiple mitophagic pathways. This function is executed primarily through the phosphorylation of several ubiquitin ligases, including its most widely studied substrate Parkin. Furthermore, the phosphorylation of both pro- and anti-apoptotic proteins by mitochondrial PINK1 acts as a pro-cellular survival signal when faced with apoptotic stimuli. Through these varied roles PINK1 directly influences functions central to cell dysfunction in neurodegenerative disease.

scholarly journals Utilizing 3D Arterial Spin Labeling to Identify Cerebrovascular Leak and Glymphatic Obstruction in Neurodegenerative Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1888
Author(s):  
Charles R. Joseph
Keyword(s):  
Neurodegenerative Disease ◽  
Therapeutic Interventions ◽  
Contrast Imaging ◽  
Neurologic Diseases ◽  
Pros And Cons ◽  
Potential Methods ◽  
Fluid Leak ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation ◽  
Do So

New approaches are required to successfully intervene therapeutically in neurodegenerative diseases. Addressing the earliest phases of disease, blood brain barrier (BBB) leak before the accumulation of misfolded proteins has significant potential for success. To do so, however, a reliable, noninvasive and economical test is required. There are two potential methods of identifying the BBB fluid leak that results in the accumulation of normally excluded substances which alter neuropil metabolism, protein synthesis and degradation with buildup of misfolded toxic proteins. The pros and cons of dynamic contrast imaging (DCI or DCE) and 3D TGSE PASL are discussed as potential early identifying methods. The results of prior publications of the 3D ASL technique and an overview of the associated physiologic challenges are discussed. Either method may serve well as reliable physiologic markers as novel therapeutic interventions directed at the vasculopathy of early neurodegenerative disease are developed. They may serve well in addressing other neurologic diseases associated with either vascular leak and/or reduced glymphatic flow.

Mechanisms of adaptation to proteinuria in adriamycin nephrosis

1993 ◽  
Vol 265 (2) ◽  
pp. F257-F263 ◽  
Author(s):  
E. J. Choi ◽  
R. C. May ◽  
J. Bailey ◽  
T. Masud ◽  
A. Dixon ◽  
...  
Keyword(s):  
Normal Growth ◽  
Whole Body ◽  
Acid Oxidation ◽  
Body Protein ◽  
Mechanisms Of Adaptation ◽  
Protein Conservation ◽  
And Control ◽  
The Impact ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

To evaluate the impact of urinary protein losses on whole body protein turnover (WBPT) independent of acidosis or uremia, we utilized a model of unilateral adriamycin nephrosis. Control rats were matched by weight to nephrotic rats and pair fed 22% protein chow for 14-18 days; urinary urea nitrogen (UUN) was measured on day 12, and leucine turnover measurement was performed on the final day. Growth rates of nephrotic and pair-fed control rats did not differ during the first 2 wk of pair feeding; thereafter, a small difference in growth could be detected. Despite an identical intake of dietary protein, UUN excretion was 29% less in the nephrotic rats (P < or = 0.02). Fasting whole body protein synthesis and degradation did not differ between nephrotic and control rats; in contrast, leucine oxidation decreased by 21% in nephrosis (P < 0.05). On the basis of near normal growth and normal rates of WBPT, we conclude that nephrotic rats fed ad libitum can adapt to the stress of continuous protein losses. A reduction in amino acid oxidation and UUN excretion were the primary mechanisms responsible for protein conservation in experimental nephrosis.

Nitrogen utilization within equine large intestine

1975 ◽  
Vol 229 (4) ◽  
pp. 1062-1067 ◽  
Author(s):  
JF Wootton ◽  
RA Argenzio
Keyword(s):  
Large Intestine ◽  
Nitrogen Utilization ◽  
Microbial Populations ◽  
Microbial Protein ◽  
Entry And Exit ◽  
Total N ◽  
Limited Protein ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation ◽  
Intestinal Compartments

The distribution of nitrogen in ligated segments of the stomach and intestine of two groups of ponies has been examined at sacrifice 2, 4, 8, and 12 h following the final 12-h scheduled feeding of diets designed to provide either 1) ample protein, or 2) limited protein plus supplemental urea as the major nitrogen source. Concentrations and total quantities of total N, NH3, urea plus NH3, and alpha-amino N were determined, and protein N was calculated by difference. Liquid marker (PEG) distribution rate constants and N concentrations were used to calculate rates of entry and exit by digesta flow for the large intestinal compartments. These values, together with measured accumulations of each constituent, allowed assessment of transitory net appearance and net disappearance within each compartment due to processes other than flow along the tract. The data suggested cyclic fluctuations of microbial populations within the large intestine, particularly the dorsal and ventral colon. These segments also were implicated as major sites of microbial protein synthesis and degradation. the former process appeared more evident in animals consuming the urea-supplemented diet.

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