Silicates (several polymorphs) SiO 2 Presented by Paul Sandlin.
Presented by s.mohammed razeeth
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Transcript of Presented by s.mohammed razeeth
PRESENTED BYS.MOHAMMED RAZEETH
INTRODUCTION Alzheimer’s disease (AD), the most
common form of age-related dementia neurodegeneration of the central
nervous system That eventually leads to a gradual
decline of cognitive function and dementia
The principal neuropathological features of AD
neurofibrillary tangleS
β-amyloid (Aβ)
NEUROFIBRILLARY TANGLES
Tau protien
Tau is a low molecular weight microtubule associated protein (MAP)
In human tau found in neurons of both the peripheral and central nervous system
MICROTUBULE
very low levels of tau expression have also been reported in glial cells
Find out by Binder et al., 1985; Cleveland et al., 1977; Couchie et al., 1992; LoPresti et al., 1995; Shin et al., 1991.
TRAFFIC SYSTEM OF THE CELL Traffic systems in the form of
cytoskeletal fibers which guide the transport of motor proteins
Two distinct fiber systems for transport
The actin microfilaments and The microtubules
Three classes of ptn involve in transport
The myosins-for the microfilament tracks
The kinesins and dyneins -for microtubule tracks
NURONS SIGNALING
FUNCTIONS OF TAU PROTIEN Intracellular vesicular transport
Organization of the actin cytoskeleton
Anchoring of phosphatases and kinases
By Buee et al., 2000;Lee et al., 2001.
Tau is best characterized for its ability to bind to
stabilize and promote the polymerization of microtubules
In Human tau encode single gene located on chromosome 17q21-22 that consists of 16 exons.
ISOFORMS Isoforms generated by alternative mRNA
splicing By Andreadis et al., 1992; Neve et al
in1986 Alternative splicing of exons (E) 2 (E2),
3(E3) and 10 (E10) It produce 6 isoforms ranging in length from 352 to 441 amino
acids
TAU
It has 3R and 4R carboxy-terminal repeats
Along with specifically identified adjacent sequences are responsible for the binding of tau to MT
(Butner and Kirschner, 1991; Gustke et al., 1994; Lee et al., 1989).
Tau is a phosphoprotein with 79 potential serine or threonine
It has (Ser/Thr) phosphorylation acceptor sites Tau phosphorylation is a normal physiological
process Which decreases tau’s binding affinity for MTs (Biernat et al., 1993; Bramblett et al., 1993;
Drechsel et al., 1992; Yoshida and Ihara, 1993)
PHOSPHORLATION SITES These phosphorylation sites can be
sub-divided into 2 groups
Residues that are phosphorylated by prolinedirected kinases
Residues that are phosphorylated by non-prolinedirected kinases
Early stages of degeneration can be detected by means of phosphorylation-sensitive antibodies
Sites occur in SP or TP motifs (7 and 10,resp.) which are preferred targets of proline-directed kinases
examples: MAPkinase, GSK-3β
tau contains 5 tyrosines (no. 18, 29, 197,310, 394)
which can be phosphorylated by Tyr-directed kinases
e.g.Y18 by the kinase fyn, Bhaskar et
al., 2005
MUTATION There are three types of mutation
reported in Tau protien
20 missense mutation 3 silent mutation 2 deletion mutation
EFFECT OF MUTATION Mutation in tau promotes tau
dysfunction and it turn leads to intracellular aggregates
There are two main pathogenic mechanisms
(i) altering the mRNA splicing of exon 10 (ii) decreasing tau-MT interactions.
TAU AGGREGATION Tau important for its abnormal behavior
in AD is the aggregation into fibers Excellent solubility which counteracts aggregation in
physiological buffers.
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