Blood–Brain Barrier Solute Carrier Transporters and Motor Neuron Disease

Abstract

Defective solute carrier (SLC) transporters are responsible for neurotransmitter dysregulation, resulting in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We provided the role and kinetic parameters of transporters such as ASCTs, Taut, LAT1, CAT1, MCTs, OCTNs, CHT, and CTL1, which are mainly responsible for the transport of essential nutrients, acidic, and basic drugs in blood–brain barrier (BBB) and motor neuron disease. The affinity for LAT1 was higher in the BBB than in the ALS model cell line, whereas the capacity was higher in the NSC-34 cell lines than in the BBB. Affinity for MCTs was lower in the BBB than in the NSC-34 cell lines. CHT in BBB showed two affinity sites, whereas no expression was observed in ALS cell lines. CTL1 was the main transporter for choline in ALS cell lines. The half maximal inhibitory concentration (IC50) analysis of [3H]choline uptake indicated that choline is sensitive in TR-BBB cells, whereas amiloride is most sensitive in ALS cell lines. Knowledge of the transport systems in the BBB and motor neurons will help to deliver drugs to the brain and develop the therapeutic strategy for treating CNS and neurological diseases.

Comparing the effects of microgravity and amyotrophic lateral sclerosis on mouse dorsal root ganglia

“…Abnormalities in sensory nerve fibers and satellite glial cells (SGCs) of sensory neurons in ALS animal models have also been reported (Guo et al, 2009;Sábado et al, 2014;Ruiz-Soto et al, 2020). Additionally, altered gene expression of solute carrier (SLC) transporters, resulting in neurodegeneration, was observed in MG and ALS mouse models (Hu et al, 2020;Paul et al, 2021;Latif and Kang, 2022;Yoshikawa et al, 2022a;b). While exposure to MG and ALS are characterized by commonly observed alterations in the motor system, only a few reports have described the molecular changes underlying sensory neuron dysfunction in ALS or after exposure to MG (Nagatomo et al, 2014;Sábado et al, 2014;Iglesias et al, 2015;Rubio et al, 2022).…”

Receptor-Assisted Nanotherapeutics for Overcoming the Blood–Brain Barrier

“…The SLC functionalization is largely affected by the astrocytic manipulation. Prime SLC subfamilies have firm emphasis on the targeting efficiency of neuroprotective drug for the treatment of neurological challenges [11]. For instance, SLC22A is highly expressed in astrocytic projections within various neuronal regions such as hippocampus, nigrostriatal axis and hypothalamus loci and is a competent transporter for the neurotransmitters like epinephrine, norepinephrine and histamine.…”

Food-Derived Peptides: Beneficial CNS Effects and Cross-BBB Transmission Strategies

“…A variety of solute carriers mediating the transport of neutral amino acids and glucose can be detected in BMECs . Common carriers include MCT, SVCT2, ASCT, CNT2, PTS-1, CTL1, etc . CMT is mainly involved in the transcellular transport of small molecular substances across the BBB, while functional peptides of high molecular weights mainly rely on RMT for crossing the BBB.…”