Human serum albumin in neurodegeneration

Abstract Serum albumin (SA) exists in relatively high concentrations, in close contact with most cells. However, in the adult brain, except for cerebrospinal fluid (CSF), SA concentration is relatively low. It is mainly produced in the liver to serve as the main protein of the blood plasma. In the plasma, it functions as a carrier, chaperon, antioxidant, source of amino acids, osmoregulator, etc. As a carrier, it facilitates the stable presence and transport of the hydrophobic and hydrophilic molecules, including free fatty acids, steroid hormones, medicines, and metal ions. As a chaperon, SA binds to and protects other proteins. As an antioxidant, thanks to a free sulfhydryl group (–SH), albumin is responsible for most antioxidant properties of plasma. These functions qualify SA as a major player in, and a mirror of, overall health status, aging, and neurodegeneration. The low concentration of SA is associated with cognitive deterioration in the elderly and negative prognosis in multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). SA has been shown to be structurally modified in neurological conditions such as Alzheimer’s disease (AD). During blood–brain barrier damage albumin enters the brain tissue and could trigger epilepsy and neurodegeneration. SA is able to bind to the precursor agent of the AD, amyloid-beta (Aβ), preventing its toxic effects in the periphery, and is being tested for treating this disease. SA therapy may also be effective in brain rejuvenation. In the current review, we will bring forward the prominent properties and roles of SA in neurodegeneration.