Parkinson’sdisease characterized by progressive loss of dopaminergic neurons and its functionsin the substantia nigra due to dysfunction of intracellular homeostasis which leadsto motor complication in PD.

The impaired ability to maintain proteinhomeostasis or proteostasis, has been implicated as a amajor culprit in PD pathogenesis.Yet, the underlying mechanisms leading to dopaminergic neuronal loss remainspoorly understood. The endoplasmic reticulum (ER) is a multifunctionalorganelle, plays a essential role for the synthesis, folding, processing andtransport of secretory and transmembrane proteins in the dopaminergic cell. Throughouttheir lifetime, neuronal cells are faced with a variety of stresses that leadto physiological and pathological stimuli can lead to disrupts ER homeostasisresulting to an accumulation of misfolded and disaggregated proteins, acondition known as ER stress (Balch et al., 2008).

In order torestore homeostasis within the ER there occurs sequential activation of theunfolded protein response (UPR) involving translational attenuation of globalprotein synthesis, transcriptional induction of genes functioning as ERchaperones, and the ER-associated degradation (ERAD) of disaggregated proteinsultimately leading to autophagy (Imai et al., 2001; Oh and Lim, 2009; Bhutia et al.,2010).Autophagy is anintracellular bulk degradative system of long-lived cytosolic organelles anddisaggregated proteins, in a non-specific manner. Autophagy deliverscytoplasmic constituents to the lysosome for degradation and converting intoenergy substrates to cellular processes, which ultimately leads to neuroprotectionand has been implicated in PD (Xiong et al., 2011). Autophagy breaks downmacromolecules and recycles their components not only to preserve cellularenergy but also to clear damaged proteins and oxidatively damaged mitochondria (Lee et al., 2012; Dodson et al.

, 2013; Zhang, 2013). Restoration or acceleration ofautophagy process improves the mitochondrial membrane potential (MMP), rarefiesreactive oxygen species (ROS) accumulation via maintaining intracellular redoxin dopaminergic neuronal cells and plays an important scavenger role againstharmful influence of toxic protein aggregates produced in rotenone-treatedcells (Dadakhujaev et al., 2010). Inaddition, intoxication of experimental models with inhibitors of complex I(rotenone, pyridaben, MPTP and its metabolite MPP+) reproduce theclinical symptoms of PD in experimental models (Higgins et al.

, 2010). Rotenone is aclassical neurotoxin with high affinity to inhibite electron transport chain-1(ETC-I). Progressive inhibition or reduced state of ETC-I leads to leakage ofelectrons, which combine with O2 to generate superoxide anions (Martinez and Greenamyre, 2012). Further leads to shunting of electrons throughETC-II, decreased ATP production, which may generate 5-7 times as excessiveproduction of ROS and antioxidant redox dysfunctions (Licker et al.,2009). Intracellular redox indicess increaseslipid and protein oxidation and induces DNA damage are important hallmarks ofPD suggesting that endogenous antioxidant protective pathways are inadequate duringdisease condition (Dexter et al., 1989; Moussaoui et al., 2000; Leviteset al.

, 2001). Furthermore, oxidatively dameged cellular organells and proteinscontributes to age-dependent accumulation of cytoplasmic debries, which leadsto dopaminergic cell death. The alternative approaches that can circumventthese limitations are needed. Although currently regulation or acceleration of ERfunction and activities of autophagy-lysosomal degradation, may inhibit or haltthe PD progression by degrading long lived, oxidatively damaged or misfoldedproteins and organelles particularly mitochondria (Pan et al., 2009; Wu et al.

, 2011). Currentpharmacological therapies for PD are inadequate, and alternative strategiessuch as stem cell therapy, neurotransplantation, and deep brain stimulation arestill in infant stage. There has been considerable interest in the developmentof neuroprotective drugs from natural origins as a therapeutic strategy for PDand importantly without adverse effects (Fukui et al., 2010). In particular plant derived monoterpenesare a class of compounds with releavent therapeutic potential and variety ofbiological activities (Bastos et al., 2010; Menezes et al., 2010; Guimaraeset al.

, 2013). Despite the fact that many studieswere performed on the function of geraniol (GE; 3,7-dimethyl-2,6-octadien-1-ol)is an acyclic monoterpene alcohol, and its posses cytoprotective andantioxidant potential in oxidative stress induced in vivomodels (Tiwari and Kakkar, 2009). But detailed molecular mechanismsthat are responsible for conferring their effects remain largely unknown (Sadraei et al., 2013; Prasad and Muralidhara, 2014). The objective of the present studyis to evaluate the protective effect of GE on rotenone-mediated PD by improve oxidativestress dependent autophagy dysfunction and ER stress in the human neuroblastmacells in SK-N-SH through up regulating its autophagic cellular clearance.

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