Gunjan J.

Increased amyloid beta (Aβ) production by sequential cleavage of the amyloid precursor protein (APP) by the β- and γ-secretases contributes to the etiological basis of Alzheimer's disease (AD). Here we hypothesize that Golgi fragmentation in AD accelerates APP trafficking and Aβ production. Furthermore, Golgi defects may perturb the proper trafficking and processing of many essential neuronal proteins.

No significant differences in genotype and allelic frequencies of MTHFR C677T polymorphism were found on comparing migraine patients with either disease controls or healthy controls. In contrast, we found synergistic role of ACE (DD)*MTHFR (CT) interaction, showing a positive association in total migraine with aura patients as well as female migraine patients with aura when compared with healthy controls.

We found that ESR1 PvuII polymorphism is a significant risk factor for migraine particularly in women and MA patients, but ESR 325 C→G polymorphism is not associated with migraine susceptibility. PROGINS polymorphism seems to play a protective role in genetic susceptibility to migraine in the North Indian population.

We could not find any significant differences in the genotype or allele frequencies in case of HT 102 T>C polymorphism between migraine patients and healthy controls (P value=0.224). No significant association was seen at allele and carrier levels.

Thus, we investigated the role of EDNRA -231 G>A and APOE HhaI polymorphism for a possible association with migraine. We found significant difference in the frequency of EDNRA AA genotype between migraine subjects when compared with HC. In the case of APOE HhaI polymorphism, E3E4 and E2E3 genotypes conferred risk when taken together in case of migraine versus HC and migraine with aura (MA) versus HC. The risk was also seen after stratification on the basis of gender in female migraineurs.

Aromatase, CYP19A1 (rs10046 and rs4646); estrogen receptors, ESR1 (rs2234693, rs1801132, rs2228480 and rs9340799) and ESR2 (rs1271572 and rs1256049) polymorphisms were selected for the present study. The study suggests that CYP19A1 polymorphisms to be the major contributing factors in migraine susceptibility instead of genetic variants of estrogen receptors.

In this study, we show that stimulation of NCAM by a function-triggering NCAM antibody results in proteolytic processing of NCAM and fak. This mutation interferes neither with NCAM cell surface expression, palmitoylation, and raft localization nor with fyn activation. The way by which the transmembrane NCAM fragment reaches the nucleus in a calmodulin- and calcium-dependent manner is by endocytotic transport via the endoplasmic reticulum and the cytoplasm.

Found the molecular mechanism of translocation of C-terminal fragment of the cell adhesion molecule, L1 and its implications. Alterations in the levels of the 70-kDa fragment during development and in the adult after spinal cord injury or in a mouse model of Alzheimer disease suggest that this fragment is functionally implicated in development, regeneration, neurodegeneration, tumorigenesis, and possibly synaptic plasticity in the mature nervous system.