scholarly journals Retrograde axonal transport of an exogenous enzyme covalently linked to B-IIb fragment of tetanus toxin

1990 ◽  
Vol 271 (1) ◽  
pp. 87-91 ◽  
Author(s):  
P Beaude ◽  
A Delacour ◽  
B Bizzini ◽  
D Domuado ◽  
M H Remy
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glucose Oxidase ◽  
Axonal Transport ◽  
Blood Brain Barrier ◽  
Tetanus Toxin ◽  
Storage Disease ◽  
Retrograde Axonal Transport ◽  
Brain Barrier ◽  
The Central Nervous System

Attempt to replace enzymes in a number of fatal lysosomal storage disease involving the central nervous system have as yet been unsuccessful owing to the impermeability of the blood/brain barrier to macromolecules. In order to treat storage disease due to enzyme deficiencies, we investigated the feasibility of transporting an enzyme into the central nervous system without crossing the blood/brain barrier. Using the B-IIb fragment of tetanus toxin (because it is involved in recognition by the nerve-cell endings), retrograde axonal transport toward the spinal cord and trans-synaptic movement, and glucose oxidase as a marker, we demonstrated that a non-toxic enzyme-vector conjugate was taken up by axon terminals. After injection into the gastrocnemius muscle, the B-IIb-glucose oxidase conjugate was detected, both histologically and electrochemically, distally to a ligature on the sciatic nerve. Thus the B-IIb fragment could serve as a vector for glucose oxidase transport into the central nervous system. It was also verified that the transported enzyme retained its activity. Transport of this 150 kDa molecule by fragment B-IIb of tetanus toxin suggests that other enzymes of a lesser molecular mass may also be transported.

Ethanolamine: A Potential Promoiety with Additional Effects in the Brain

2020 ◽  
Vol 19 ◽  
Author(s):  
Asfree Gwanyanya ◽  
Christie Nicole Godsmark ◽  
Roisin Kelly-Laubscher
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Design ◽  
Cell Signaling ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
The Central Nervous System ◽  
Bioactive Molecule ◽  
Positive Functions ◽  
The Brain

Abstract: Ethanolamine is a bioactive molecule found in several cells, including those in the central nervous system (CNS). In the brain, ethanolamine and ethanolamine-related molecules have emerged as prodrug moieties that can promote drug movement across the blood-brain barrier. This improvement in the ability to target drugs to the brain may also mean that in the process ethanolamine concentrations in the brain are increased enough for ethanolamine to exert its own neurological ac-tions. Ethanolamine and its associated products have various positive functions ranging from cell signaling to molecular storage, and alterations in their levels have been linked to neurodegenerative conditions such as Alzheimer’s disease. This mini-review focuses on the effects of ethanolamine in the CNS and highlights the possible implications of these effects for drug design.

scholarly journals Permeability of the Blood-Brain Barrier and Transport of Nanobodies Across the Blood-Brain Barrier

2018 ◽  
Vol 62 (1) ◽  
pp. 59-66 ◽  
Author(s):  
I. Širochmanová ◽  
Ľ. Čomor ◽  
E. Káňová ◽  
I. Jiménez-Munguía ◽  
Z. Tkáčová ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Chemical Properties ◽  
Cost Effective ◽  
Central Nervous System Disease ◽  
Brain Barrier ◽  
Promising Alternative ◽  
Blood Brain ◽  
The Central Nervous System

Abstract The presence of a blood-brain barrier (BBB) and a blood-cerebrospinal fluid barrier presents animmense challenge for effective delivery of therapeutics to the central nervous system. Many potential drugs, which are effective at their site of action, have failed due to the lack of distribution in sufficient quantity to the central nervous system (CNS). In consequence, many diseases of the central nervous system remain undertreated. Antibodies, IgG for example, are difficult to deliver to the CNS due to their size (~155 kDa), physico-chemical properties and the presence of Fc receptor on the blood-brain barrier. Smaller antibodies, like the recently developed nanobodies, may overcome the obstacle of the BBB and enter into the CNS. The nanobodies are the smallest available antigen-binding fragments harbouring the full antigenbinding capacity of conventional antibodies. They represent a new generation of therapeutics with exceptional properties, such as: recognition of unique epitopes, target specificity, high affinity, high solubility, high stability and high expression yields in cost-effective recombinant production. Their ability to permeate across the BBBmakes thema promising alternative for central nervous system disease therapeutics. In this review, we have systematically presented different aspects of the BBB, drug delivery mechanisms employed to cross the BBB, and finally nanobodies — a potential therapeutic molecule against neuroinfections.

Sign in / Sign up

Export Citation Format

Share Document