INTRODUCTION adult rat[2]. Large numbers of HLA-DR positive microglia

INTRODUCTION

Parkinson’s
disease (PD) is a progressive neurodegenerative disease of global health
concern where dopaminergic neurons start to degenerate. The ‘non-calcemic’
functions of vitamin D is associated with healthy function of CNS 1. Thus the
question arises whether the Parkinson’s disease is largely due to vitamin D
deficiency! If so, proper therapeutic use of vitamin D can cure, or, at least,
delay the progression of the disease.

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BACKGROUND
OF THE PROBLEM

Vitamin
D deficiency and PD is related in different ways. Low bone mineral density and
decreased vitamin D level are major characteristics of PD patients2.

Receptors
for neurotrophic factors (viz. BDNF, GDNF, CDNF) is reduced in the substantia
nigra (SN) of PD patients. Calcitriol regulates the expression of low affinity
neurotrophic receptors and increases GDNF mRNA level in adult rat2.

Large
numbers of HLA-DR positive microglia were detected in the SN of PD patients. Calcitriol
decreases interferon gamma induced HLA-DR antigen expression on normal and
transformed human keratinocytes2.

Vitamin
D receptor (VDR) mRNA is a potential blood marker of PD2.

CYP2D6
enzyme (converts vitamin D3 into 25-OHD) coding region deletion shows PD like
symptoms in mice2.

Overexpression
of poly(ADP-Ribose) polymerase-1 (PARP-1) has been reported in the dopaminergic
neurones of PD patients. Calcitriol treatment can decrease PARP-1 in NB4 cells (acute
promyelotic leukemia cell)2.

Calcitriol
decreases L-type voltage sensitive calcium channels in aged rats,  neuronal vulrability, and control Ca2+ dysregulation2.

Nerve
Growth factors increases survival of dopaminergic grafts, rescues nigral
dopaminergic neurones and restores motor dysfunction in a rat model of PD. In
vitro, calcitriol regulates the expression of NGF gene in Schwann cells2.

Matrix
metalloproteinases-3 (MMP-3) expression increases during LPS-induced dopamine
neurotoxicity. MMP-3 is elevated in MPTP induced parkinsonism in mice.
Calcitriol downregulates MMP-3 levels in keratinocytes2.

Increase
of Prostaglandin E2 level and over-expression of COX-2 is reported in PD.
Calcitriols regulates the expression of several key genes in this pathway2.

Oxidative
stress and increased lipid peroxydation is reported in the SN of PD patients. A
significant increase in the nitrite content was reported in polymorphonuclear leucocytes
of PD patients. Calcitriol increases intracellular antioxidant Glutathione
pools and significantly nitrite production induced by LPS2.

Low
bone mineral density and increased bone turnover makers (bone alkaline
phosphatase and urinary N-terminal telopeptide of type 1 collagen) is also reported
in PD patients. 2.