The document discusses tight junctions in the blood-brain barrier. Tight junctions form the basic structure of the blood-brain barrier and limit paracellular permeability through the tight junction proteins claudins, junctional adhesion molecules (JAMs), and cytoplasmic plaque proteins. Claudins control sealing and channels for paracellular transport. JAMs undergo homophilic binding between cells. The cytoplasmic plaque includes zonula occludens proteins and cingulin which link tight junction proteins to actin. Disruptions in tight junction proteins are associated with several neurological diseases including Alzheimer's, stroke, epilepsy, and Parkinson's disease.

1. Yograj Banteria

2. Tight Junctions in Blood Brain Barrier:-
• Blood-brain barrier (BBB) is a dynamic interference that regulates
the nutrition and toxic substance in and out of the central nervous
system (CNS), and plays a crucial role in maintaining a stable
circumstance of the CNS.
• Tight junctions among adjacent cells form the basic structure of BBB
to limiting paracellular permeability. In the present, the constituents
of tight junction proteins are depicted, together with the regulation of
tight junction under stimulation and in pathological conditions.

4. Tight Junction Proteins:-
• Tight junction, one of the type of cell-cell junctions, controls the
paracellular permeability across the lateral intercellular space and
maintains the cell polarity.
• Tight junctions consist of transmembrane proteins: members of tight
junction-associated MARVEL protein (TAMP) family, claudins and
junctional adhesion molecules (JAMs), and various cytoplasmic
proteins that are necessary for the correct organization of the
integral membrane components of the junction.

6. Junctional Adhesion Molecules:-
• Junctional adhesion molecules (JAMs) are members of an
immunoglobulin subfamily expressed by leukocytes and platelets as
well as by epithelial and endothelial cells, in which they localize to
cell-cell contacts and are specifically enriched at tight junctions.
• JAM-A, JAM-B and JAM-C undergo homophilic binding, molecules
on adjacent cells interacting in trans.
• Whether the homophilic interactions between JAMs contribute to cell
adhesion is not clear: this has yet to be described in cell aggregation
assays.
• The homophilic interactions between JAMs have functional
consequences for cell-cell contact integrity.

8. Claudins Protein Family:-
• The ECLs interact laterally and with counterparts of the neighboring cell
and by this achieve a general sealing function.
• Two TJ protein families can be distinguished, claudins, comprising 27
members in mammals, and TJ-associated MARVEL proteins (TAMP),
comprising occludin, tricellulin, and MarvelD3. They are linked to a
multitude of TJ-associated regulatory and scaffolding proteins.
• The major TJ proteins are classified according to the physiological role
they play in enabling or preventing paracellular transport.
• Many TJ proteins have sealing functions (claudins 1, 3, 5, 11, 14, 19, and
tricellulin).
• In contrast, a significant number of claudins form channels across TJs
which feature selectivity for cations (claudins 2, 10b, and 15), anions
(claudin-10a and -17), or are permeable to water (claudin-2).
• For several TJ proteins, function is yet unclear as their effects on epithelial
barriers are inconsistent (claudins 4, 7, 8, 16, and occludin).

10. Cytoplasmic Plaques( Desmosomes ):-
• The cytoplasmic plaque of tight junctions is formed by different
components that include adapters, such as zonula occludens (ZO),
multi-PDZ domain protein 1 as well as Cingulin and other proteins
like signaling molecules, kinases and polarity complexes .
• Prominent components of tight junction plaque are the zonula
occludens proteins ZO-1, -2 and -3 .
• They belong to the MAGUK (membrane-associated guanylate
kinase-like homologs) family and contain three PDZ domains, one
SH3 domain and one guanylate kinase-like (GUK) domain.
• Another adapter, cingulin links tight junction proteins to the actin
and myosin .

12. Neurological Diseases :
• Alzheimer's Disease--hyper- phosphorylated Tau protein in neuronal cell
bodies
• Stroke-- Src-mediated tyrosine phosphorylation of occludin.
• Epilepsy- immunoreactivity for tight junction proteins, ZO-1 and occludin.
• Multiple Sclerosis-- lack of ZO-1 and occludin .
• Parkinson’s Disease-decreased expression of the tight junction proteins ZO-1
and occludin in the striatum that was associated with disruption of the blood–
brain barrier in MPTP-induced mouse model of Parkinson’s disease.
• Proteins forming tight junctions are expressed in endothelial cell of
brain vasculature and are crucial component of blood-brain barrier.
• Additionally, few reports indicate other than blood–brain barrier
localization of some of these proteins, possibly not even restricted to
tight junctions.
• If it is of any relevance to brain pathology remains to be studied.

13. Parkinson’s Disease