Therapeutic potential for peripheral clearance of misfolded brain proteins

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...

Hepatic clearance refers to the volume of blood cleared of a drug by the liver per unit of time. It plays a crucial role in drug metabolism and elimination. While hepatic clearance is commonly estimated by subtracting renal clearance from total body clearance, other pathways, such as pulmonary or biliary clearance, may also contribute. However, these pathways are generally less significant than hepatic and renal clearance.
Most drugs undergo restrictive clearance, which is proportional to the...

The glomerular filtration rate (GFR) is a critical marker of kidney function, reflecting the efficiency of filtration by the glomeruli. Renal clearance of specific substances, such as inulin or creatinine, is commonly used to measure GFR.
Renal clearance refers to the volume of plasma cleared of a specific substance, such as creatinine, per unit of time. To measure clearance, urine samples are collected over a 24-hour period during each bladder voiding, followed by a single blood sample at the...

Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick.  Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA...

Drug elimination refers to drug removal from the body, either through urine or bile, by the kidneys or liver, respectively. A pharmacokinetic parameter, drug clearance, measures the efficiency of drug removal from the bloodstream within a specific time frame. It is calculated as the rate at which a drug is eliminated from plasma divided by the drug's concentration in plasma.
Drug clearance is not limited to renal excretion but encompasses all organs involved in drug elimination, including...