Dopaminergic Activity Research Articles

Analysis of individual differences in neurofeedback training illuminates successful self-regulation of the dopaminergic midbrain

The dopaminergic midbrain is associated with reinforcement learning, motivation and decision-making – functions often disturbed in neuropsychiatric disorders. Previous research has shown that dopaminergic midbrain activity can be endogenously modulated via neurofeedback. However, the robustness of endogenous modulation, a requirement for clinical translation, is unclear. Here, we examine whether the activation of particular brain regions associates with successful regulation transfer when feedback is no longer available. Moreover, to elucidate mechanisms underlying effective self-regulation, we study the relation of successful transfer with learning (temporal difference coding) outside the midbrain during neurofeedback training and with individual reward sensitivity in a monetary incentive delay (MID) task. Fifty-nine participants underwent neurofeedback training either in standard (Study 1 N = 15, Study 2 N = 28) or control feedback group (Study 1, N = 16). We find that successful self-regulation is associated with prefrontal reward sensitivity in the MID task (N = 25), with a decreasing relation between prefrontal activity and midbrain learning signals during neurofeedback training and with increased activity within cognitive control areas during transfer. The association between midbrain self-regulation and prefrontal temporal difference and reward sensitivity suggests that reinforcement learning contributes to successful self-regulation. Our findings provide insights in the control of midbrain activity and may facilitate individually tailoring neurofeedback training.

Herbal Moieties and its effect on Parkinsonism: A New Prospective

Parkinson’s disease is a brain disease that leads to stiffness, shaking, and problems with walking, balance of coordination, and brain injury. It occurs when nerve cells or neurons that produce an important brain channel known as dopamine and control the movements in an area of the brain is impaired and die. Parkinson’s symptoms usually begin gradually and get worse over times. Age is the one clear risk factor for this disease. A person with Parkinson’s disease may have clumps of proteins known as alpha synuclein or Lewy bodies in their brain. There is no cure for Parkinson’s disease, the aim of medical management of Parkinson’s disease to restore the proper balance of dopaminergic and cholinergic activities in the brain in order to relieve symptoms. This review presents a brief overview of scientific basis that support the plant derived natural products and their constituents for the treatment of underlying neuronal degeneration observed in Parkinson’s disease. The neuroprotective effects exhibited by these medicinal plants and their constituents are considered to be due to their ability to modulate; glutathione, superoxide dismutase and catalase in the brain, which all are disrupted in the PD brain. Keywords: PD, Indian Herbs

Gambaran Caffeine Addiction Pada Ibu Rumah Tangga

Caffeine is still a popular processed food or drink among teenagers and adults, as well as housewives who still have the habit of consuming caffeine such as coffee or tea. Caffeine as an antagonist at the adenosine receptor will stimulate dopaminergic activity which will cause psychostimulant properties, namely providing a wakeful and arousing effect which can then lead to potential addiction or addiction to caffeine. Consuming caffeine in excess of the daily limit can cause side effects including anxiety, insomnia, increased heart rate, and gastrointestinal disturbances. Therefore, the purpose of this study was to determine the description of caffeine addiction in housewives. The research method using descriptive analysis with sampling using cross sectional technique obtained a sample of 33 people. The data was obtained from filling out questionnaires by respondents about caffeine addiction, then the questionnaire was tested for validity and reliability. The results obtained from the validity test of 9 questionnaire questions, namely r count > r table (0.344), it can be concluded that the questionnaire is valid. Furthermore, the reliability test on the questionnaire obtained the results of the Cronbach alpha value of 0.933 which means > 0.6 so it can be concluded that the questionnaire in this study is said to be reliable. To find out the description of caffeine addiction in respondents, univariate analysis with SPSS showed that most respondents experienced caffeine addiction in the moderate category, namely 29 respondents (87.9%), and 4 respondents (12.1%) experienced caffeine addiction in mild category. The conclusion of this study is that housewives experience caffeine addiction in the moderate category, namely 29 respondents. The importance of limiting daily caffeine intake to minimize the risk of addiction to caffeine and the side effects caused by caffeine.

Alpha1-adrenergic receptor blockade in the ventral tegmental area attenuates acquisition of cocaine-induced pavlovian associative learning.

Activity of the alpha1-adrenergic receptor (α1-AR) in the ventral tegmental area (VTA) modulates dopaminergic activity, implying its modulatory role in the behavioral functions of the dopamine (DA) system. Indeed, intra-VTA α1-AR blockade attenuates conditioned stimulus dependent behaviors such as drug seeking responses signifying a role of the noradrenergic signaling in the VTA in conditioned behaviors. Importantly, the role of the VTA α1-AR activity in Pavlovian associative learning with positive outcomes remains unknown. Here, we aimed to examine how intra-VTA α1-AR blockade affects acquisition of cocaine-induced Pavlovian associative learning in the conditioned place preference (CPP) paradigm. The impact of α1-AR blockade on cocaine-reinforced operant responding and cocaine-evoked ultrasonic vocalizations (USVs) was also studied. In addition, both α1-AR immunoreactivity in the VTA and its role in phasic DA release in the nucleus accumbens (NAc) were assessed. We demonstrated cellular localization of α1-AR expression in the VTA, providing a neuroanatomical substrate for the α1-AR mechanism. We showed that prazosin (α1-AR selective antagonist; 1 μg/0.5 μl) microinfusion attenuated electrically evoked DA transients in the NAc and dose-dependently (0.1–1 μg/0.5 μl) prevented the acquisition of cocaine CPP but did not affect cocaine-reinforced operant responding nor cocaine-induced positive affective state (measured as USVs). We propose that the VTA α1-AR signaling is necessary for the acquisition of Pavlovian associative learning but does not encode hedonic value. Thus, α1-AR signaling in the VTA might underlie salience encoding of environmental stimuli and reflect an ability of alerting/orienting functions, originating from bottom-up information processing to guide behaviors.

Dopamine activity on the perceptual salience for recognition memory.

To survive, animals must recognize relevant stimuli and distinguish them from inconspicuous information. Usually, the properties of the stimuli, such as intensity, duration, frequency, and novelty, among others, determine the salience of the stimulus. However, previously learned experiences also facilitate the perception and processing of information to establish their salience. Here, we propose “perceptual salience” to define how memory mediates the integration of inconspicuous stimuli into a relevant memory trace without apparently altering the recognition of the physical attributes or valence, enabling the detection of stimuli changes in future encounters. The sense of familiarity is essential for successful recognition memory; in general, familiarization allows the transition of labeling a stimulus from the novel (salient) to the familiar (non-salient). The novel object recognition (NOR) and object location recognition (OLRM) memory paradigms represent experimental models of recognition memory that allow us to study the neurobiological mechanisms involved in episodic memory. The catecholaminergic system has been of vital interest due to its role in several aspects of recognition memory. This review will discuss the evidence that indicates changes in dopaminergic activity during exposure to novel objects or places, promoting the consolidation and persistence of memory. We will discuss the relationship between dopaminergic activity and perceptual salience of stimuli enabling learning and consolidation processes necessary for the novel-familiar transition. Finally, we will describe the effect of dopaminergic deregulation observed in some pathologies and its impact on recognition memory.

Studying cognitive function in patients with a long-standing diagnosis of SWEDD

IntroductionThe cognitive profile of patients with longstanding clinical Parkinsonism possessing scans without evidence of dopaminergic deficit (SWEDD) remains unclear from previous studies. MethodsWe studied 47 patients recruited in the Parkinson's Progression Markers Initiative with SWEDD as baseline diagnosis. They were subdivided by final clinical diagnoses after a 2-year follow-up period into 25 patients with either clinical evidence of Parkinson's Disease (PD) or unclassified parkinsonism and normal SPECT imaging (“true SWEDDs”), 6 patients with a psychogenic illness exhibiting Parkinsonism, 6 patients who had phenoconverted to PD based on reduced striatal dopaminergic activity on imaging, and 10 patients with another tremulous condition. Cognitive symptoms were compared between these subgroups, as well as with 62 PD patients and 195 healthy controls (HCs), at baseline and follow-ups. ResultsA significant difference in working memory was found between true SWEDDs and HCs (P = 0.009), but not true SWEDDs and PD patients (P = 0.432), nor PD patients and HCs (P = 0.154). The prevalence of attentional impairment was also significantly different between the three groups (P < 0.001). SWEDD subgroups possessed similar cognitive symptoms irrespective of their final clinical diagnosis. Psychogenic, phenoconverted and tremulous SWEDDs also possessed stable cognitive symptoms over the 2-year period whilst true SWEDDs, PD patients and HCs experienced significant changes in working memory. ConclusionsOur results, particularly relating to working memory and attention, add to the knowledge of other true SWEDD non-motor symptoms to facilitate earlier diagnosis and improved management strategies for these patients.

A mechanistic model of ADHD as resulting from dopamine phasic/tonic imbalance during reinforcement learning.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children. Although the involvement of dopamine in this disorder seems to be established, the nature of dopaminergic dysfunction remains controversial. The purpose of this study was to test whether the key response characteristics of ADHD could be simulated by a mechanistic model that combines a decrease in tonic dopaminergic activity with an increase in phasic responses in cortical-striatal loops during learning reinforcement. To this end, we combined a dynamic model of dopamine with a neurocomputational model of the basal ganglia with multiple action channels. We also included a dynamic model of tonic and phasic dopamine release and control, and a learning procedure driven by tonic and phasic dopamine levels. In the model, the dopamine imbalance is the result of impaired presynaptic regulation of dopamine at the terminal level. Using this model, virtual individuals from a dopamine imbalance group and a control group were trained to associate four stimuli with four actions with fully informative reinforcement feedback. In a second phase, they were tested without feedback. Subjects in the dopamine imbalance group showed poorer performance with more variable reaction times due to the presence of fast and very slow responses, difficulty in choosing between stimuli even when they were of high intensity, and greater sensitivity to noise. Learning history was also significantly more variable in the dopamine imbalance group, explaining 75% of the variability in reaction time using quadratic regression. The response profile of the virtual subjects varied as a function of the learning history variability index to produce increasingly severe impairment, beginning with an increase in response variability alone, then accumulating a decrease in performance and finally a learning deficit. Although ADHD is certainly a heterogeneous disorder, these results suggest that typical features of ADHD can be explained by a phasic/tonic imbalance in dopaminergic activity alone.

Review: Subjective Time Perception, Dopamine Signaling, and Parkinsonian Slowness.

The association between idiopathic Parkinson's disease, a paradigmatic dopamine-deficiency syndrome, and problems in the estimation of time has been studied experimentally for decades. I review that literature, which raises a question about whether and if dopamine deficiency relates not only to the motor slowness that is an objective and cardinal parkinsonian sign, but also to a compromised neural substrate for time perception. Why does a clinically (motorically) significant deficiency in dopamine play a role in the subjective perception of time's passage? After a discussion of a classical conception of basal ganglionic control of movement under the influence of dopamine, I describe recent work in healthy mice using optogenetics; the methodology visualizes dopaminergic neuronal firing in very short time intervals, then allows for correlation with motor behaviors in trained tasks. Moment-to-moment neuronal activity is both highly dynamic and variable, as assessed by photometry of genetically defined dopaminergic neurons. I use those animal data as context to review a large experimental experience in humans, spanning decades, that has examined subjective time perception mainly in Parkinson's disease, but also in other movement disorders. Although the human data are mixed in their findings, I argue that loss of dynamic variability in dopaminergic neuronal activity over very short intervals may be a fundamental sensory aspect in the pathophysiology of parkinsonism. An important implication is that therapeutic response in Parkinson's disease needs to be understood in terms of short-term alterations in dynamic neuronal firing, as has already been examined in novel ways—for example, in the study of real-time changes in neuronal network oscillations across very short time intervals. A finer analysis of a treatment's network effects might aid in any effort to augment clinical response to either medications or functional neurosurgical interventions in Parkinson's disease.

A gradual temporal shift of dopamine responses mirrors the progression of temporal difference error in machine learning.

A large body of evidence has indicated that the phasic responses of midbrain dopamine neurons show a remarkable similarity to a type of teaching signal (temporal difference (TD) error) used in machine learning. However, previous studies failed to observe a key prediction of this algorithm: that when an agent associates a cue and a reward that are separated in time, the timing of dopamine signals should gradually move backward in time from the time of the reward to the time of the cue over multiple trials. Here we demonstrate that such a gradual shift occurs both at the level of dopaminergic cellular activity and dopamine release in the ventral striatum in mice. Our results establish a long-sought link between dopaminergic activity and the TD learning algorithm, providing fundamental insights into how the brain associates cues and rewards that are separated in time.

The impulsive horse: Comparing genetic, physiological and behavioral indicators to those of human addiction.

Stress and genotype elicit changes in impulse control in a range of species that are attributable to adaptations in both the central and peripheral nervous system. We examined aspects of this mechanism in the horse by assessing the effect of a dopamine receptor genotype (DRD4) and central dopaminergic tone (measured via spontaneous blink rate [SBR] and behavioral initiation rate [BIR]), on measures of impulsivity, compulsivity (3-choice serial reaction time task) and sympathetic/ parasympathetic system balance (heart rate variability [HRV]). Genotype did not have a significant effect on any of the parameters measured. SBR but not BIR correlated significantly with levels of impulsivity. There was no clear association of HRV parameters with either measures of central dopaminergic activity or impulsivity/compulsivity. Overall, some elements of the data suggest that the horse may be a useful animal model for assessing the genetic and environmental factors that lead to the physiological and behavioral phenotype of human addiction, particularly when considering the relationship between central dopaminergic tone and impulsivity.

SPION nanoparticles for delivery of dopaminergic isoquinoline and benzazepine derivatives

Superparamagnetic iron nanoparticles (SPIONs) have become one of the most useful colloidal systems in nanomedicine. We report here the preparation of new hybrid core@shell systems based on SPION nanoparticles coated with a SiO2 shell (SPION@SiO2) and functionalized with carboxyl groups (SPION@SiO2-COOH). A series of new N-alkylamino- and N-alkylamido-terminated 1-phenyl- tetrahydroisoquinolines (THIQs) and 3-tetrahydrobenzazepines (THBs) derivatives presenting -SMe and -Cl groups, respectively, with potential dopaminergic activity, are synthesized and incorporated to the hybrid system. We include the synthetic details for THIQs and THBs derivatives preparation and investigate the influence of the terminal-functional group as well as the number of carbon atoms linked to THIQ and THB molecules during the coupling to the SPION@SiO2-COOH. Nuclear magnetic resonance (NMR) and electron ionization mass spectrometry (EI-MS) are used to characterize the synthesized THIQs and THBs. High-angle annular dark-field transmission electron microscopy (HAADF-TEM), energy dispersive X-ray transmission electron microscopy (EDX-TEM), and proton high-resolution magic angle spinning NMR spectroscopy1H HRMAS-NMR) are used to confirm the presence of THB and THIQ molecules onto the surface of the nanoparticles. The hybrid SPION@SiO2-THIQ and THB systems show significant activity toward the D2 receptor, reaching Ki values of about 20 nM, thus having potential application in the treatment of central nervous system (CNS) diseases.

Ketogenic therapy for Parkinson's disease: A systematic review and synthesis without meta-analysis of animal and human trials

ObjectiveThe aim of the present systematic review was to assess the efficacy of ketogenic therapy in Parkinson's disease (PD), using all available data from randomized controlled trials (RCTs) on humans and animal studies with PD models. DesignSystematic review of in vivo studies. MethodsStudies related to the research question were identified through searches in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, clinicaltrials.gov and the gray literature, from inception until November 2021. Rayyan was employed to screen and identify all studies fulfilling the inclusion criteria. Cochrane's revised Risk of Bias 2.0 and SYRCLE tools evaluated bias in RCTs and animal studies, respectively. An effect direction plot was developed to synthesize the evidence of the RCTs. ResultsTwelve studies were identified and included in the qualitative synthesis (4 RCTs and 8 animal trials). Interventions included ketogenic diets (KDs), supplementation with medium-chain triglyceride (MCT) oil, caprylic acid administration and ketone ester drinks. The animal research used zebrafish and rodents, and PD was toxin-induced. Based on the available RCTs, ketogenic therapy does not improve motor coordination and functioning, cognitive impairment, anthropometrics, blood lipids and glycemic control, exercise performance or voice disorders in patients with PD. The evidence is scattered and heterogenous, with single trials assessing different outcomes; thus, a synthesis of the evidence cannot be conclusive regarding the efficacy of ketogenic therapy. On the other hand, animal studies tend to demonstrate more promising results, with marked improvements in locomotor activity, dopaminergic activity, redox status, and inflammatory markers. ConclusionsAlthough animal studies indicate promising results, research on the effect of ketogenic therapy in PD is still in its infancy, with RCTs conducted on humans being heterogeneous and lacking PD-specific outcomes. More studies are required to recommend or refute the use of ketogenic therapy in PD.

D2 receptor antagonism enhances cocaine-induced behavioral sensitization in female, but not male Japanese quail ( Coturnix japonica ).

Sex differences in cocaine-induced behaviors are well established. In rodents, females show enhanced locomotion to cocaine over multiple trials compared with males, a behavioral response known as sensitization. Estradiol enhances cocaine-induced sensitization in female rats by agonizing dopaminergic activity within the brain. In female quail, cocaine does not increase locomotion regardless of increased estradiol. A higher D2:D1 dopamine receptor ratio in quail compared with rodents may explain this sex and species difference. The goal of the present work was to investigate the role of D2 receptors in cocaine-induced locomotion and sensitization in Japanese quail and to determine whether a greater D2 receptor availability contributed to the lack of cocaine-induced sensitization in female quail found in previous studies. Male and female quail were administered 0, 0.03, 0.05, or 0.07 mg/kg of eticlopride (Eti) followed by 10 mg/kg of cocaine or saline then immediately placed in open-field chambers. Distance traveled was recorded for 30 min daily for 7 days. In female quail, cocaine-induced sensitization was observed with 0.03 or 0.05 mg/kg Eti, but not in cocaine-only females. In male quail, cocaine-induced sensitization was observed similar to previous research. However, Eti did not enhance cocaine-induced locomotion or produce sensitization in male quail. The D2 receptor likely mediates cocaine's motor stimulating effects in quail. In females, this effect is more pronounced. Since high D2 availability is protective against stimulant abuse, Japanese quail may be a useful model for investigating the role of the D2 receptor in cocaine addiction, but further research is needed.

Dopamine and oxytocin and their relevance for attachment: A gene x gene interaction study

An interaction between dopamine and oxytocin has been shown in several human and animal studies. Effects of oxytocin on dopaminergic activity depend on the location of dopaminergic neurons resulting in increased prosocial or decreased exploratory behavior. Both components are associated with attachment and the knowledge so far justifies investigating the interaction on a molecular genetic level with respect to adult attachment. A total number of N = 545 participants were genotyped for COMT rs4680 and OXTR rs53576. The Attachment-Style-Questionnaire (ASQ) was used to measure adult attachment. The interaction of COMT and OXTR yielded a significant result for the ASQ. The combination of the COMT-Met/Met and OXTR-AA genotype yielded significantly higher Need for Approval and Relationships as Secondary. The results confirm the interaction between dopamine and oxytocin for certain aspects of adult attachment as a “behavioral phenotype” and will be discussed with respect to a better understanding of the neurobiological underpinnings of attachment.

Efficient coding of cognitive variables underlies dopamine response and choice behavior.

Reward expectations based on internal knowledge of the external environment are a core component of adaptive behavior. However, internal knowledge may be inaccurate or incomplete due to errors in sensory measurements. Some features of the environment may also be encoded inaccurately to minimize representational costs associated with their processing. In this study, we investigated how reward expectations are affected by features of internal representations by studying behavior and dopaminergic activity while mice make time-based decisions. We show that several possible representations allow a reinforcement learning agent to model animals' overall performance during the task. However, only a small subset of highly compressed representations simultaneously reproduced the co-variability in animals' choice behavior and dopaminergic activity. Strikingly, these representations predict an unusual distribution of response times that closely match animals' behavior. These results inform how constraints of representational efficiency may be expressed in encoding representations of dynamic cognitive variables used for reward-based computations.

Aripiprazol and Hypersexuality: when partial is to much

IntroductionA growing number of published cases has showed that hypersexual behavior may arise with treatment with second-generation antipsychotics, including aripiprazole and olanzapine. Aripiprazole is a second-generation antipsychotic commonly used to treat schizophrenia and bipolar disorder. It has a unique pharmacologic profile acting as a partial agonist of the dopamine D2 receptor, as a partial agonist at the 5-HT1A receptor, and as an antagonist at the 5-HT2A receptor. Literature shows that medication with partial dopaminergic agonistic activity can cause compulsive behaviors, such as pathological gambling, compulsive eating, compulsive shopping, and hypersexuality. Although it is difficult to predict who would develop these behaviors, the literature suggests that patients at a higher risk of developing impulsive behaviors include those with a personal or family history of obsessive-compulsive disorder, impulse control disorder, bipolar disorder, impulsive personality, alcoholism, drug abuse, or other addictive behaviors.ObjectivesHere, we present a case of a 32-year-old male who developed hypersexuality symptoms after receiving aripiprazole as treatment for bipolar disorder.MethodsWe have done a literature review using the MeSH terms Aripiprazole and hypersexuality in the “PubMed”.ResultsAfter switching Aripiprazole to Risperidone the hypersexuality symptoms started to decrease and got almost complete relief after 2 weeks.ConclusionsThis case highlights the rare hypersexuality side effect that can arise in patients receiving aripiprazole for bipolar disorder treatment. Clinicians should be aware of the increased risk of hypersexuality and other impulsive behaviors as they can significantly impair a patient’s daily functioning.DisclosureNo significant relationships.

Cera Flava Improves Behavioral and Dopaminergic Neuronal Activities in a Mouse Model of Parkinson’s Disease

Cera Flava Improves Behavioral and Dopaminergic Neuronal Activities in a Mouse Model of Parkinson’s Disease

Adolescent sleep shapes social novelty preference in mice.

Sleep disturbances frequently occur in neurodevelopmental disorders such as autism, but the developmental role of sleep is largely unexplored, and a causal relationship between developmental sleep defects and behavioral consequences in adulthood remains elusive. Here, we show that in mice, sleep disruption (SD) in adolescence, but not in adulthood, causes long-lasting impairment in social novelty preference. Furthermore, adolescent SD alters the activation and release patterns of dopaminergic neurons in the ventral tegmental area (VTA) in response to social novelty. This developmental sleep function is mediated by balanced VTA activity during adolescence; chemogenetic excitation mimics, whereas silencing rescues, the social deficits of adolescent SD. Finally, we show that in Shank3-mutant mice, improving sleep or rectifying VTA activity during adolescence ameliorates adult social deficits. Together, our results identify a critical role of sleep and dopaminergic activity in the development of social interaction behavior.

DNSP‐11 reduces 6‐OHDA‐induced caspase 3/7 activation in an SH‐SY5Y cell model: Potential Role of ERK signaling pathway?

Glial cell line‐derived neurotrophic factor (GDNF) has been shown to be a promising therapeutic molecule for treating Parkinson’s disease (PD). However, because of the failure of GDNF infusion in clinical trials, due to its poor bio‐distribution, there was a need to develop other molecules with similar properties to GDNF that have improved bioavailability and administration. Dopamine neuron stimulating peptide‐11 (DNSP‐11) is a synthetic, amidated 11‐amino acid neuroactive peptide derived from the human proGDNF domain. DNSP‐11 has been shown to protect dopaminergic cells in vitro and restore dopaminergic activity in vivo. Therefore, the objective of our study was to test if DNSP‐11 protects human dopaminergic neuroblastoma SH‐SY5Y cells against 6‐OHDA induced toxicity and to elucidate the protective mechanism of action. DNSP‐11 reduced the 6‐OHDA–induced increase in caspase‐3/7 activity in SH‐SY5Y cells at early time points, indicating possible protection against apoptosis. DNSP‐11 also activated the cell survival signaling pathways, ERK1, 2, and 5 in SH‐SY5Y cells. In addition, a single injection of DNSP‐11 in adult rat striatum leads to modulation of these ERK proteins in the substantia nigra. Overall, the results indicate that DNSP‐11 protects human dopaminergic neuroblastoma cells against apoptotic cell death and activates neuroprotective ERK signaling pathways, suggesting its potential therapeutic role in Parkinson’s disease (PD).

Parkinson's Disease

Parkinson’s disease (PD) is a neurodegenerative disease that involves a progressive loss of dopaminergic neurons within the substantia nigra. Patients with PD experience a loss of motor function over time. In normal patients, muscle contractions are driven by action potentials through the binding of the neurotransmitter dopamine. Disruptions to dopaminergic activity would thus result in less efficient contractions. Patients with Parkinson’s can experience akinesia, tremors and other motor dysfunction.Glucocerebrosidase (GCase), specifically β‐GCase, is a lysosomal enzyme involved in sphingolipid metabolism. β‐GCase falls under the hydrolase classification, allowing it to catabolize glucosylceramide (GlcCer) into glucose and ceramide. β‐GCase consists of 497 amino acid glycoproteins within its four domains. The glucocerebrosidase gene (GBA) mutations are often associated with Gaucher disease. However, β‐GCase synthesized from mutated GBA1 is often studied as a biomarker for PD susceptibility. In a healthy cell with the non‐mutated GBA gene, the GBA gene would be transcribed into mRNA and then transported out to the rough Endoplasmic Reticulum, where GCase is then synthesized. Lysosomal integral membrane protein‐2 (LIMP2) is a protein that transports GCase through the Golgi Apparatus and transfers the β‐GCase into a late endosome. When the late endosome fuses with a lysosome, where β‐GCase can hydrolyze its substrates. Mutated β‐GCase may affect this autophagy pathway.This research will explore how mutated β‐GCase may disturb lysosomal functions, which would consequently lead to the aggregation of alpha‐synuclein (ASN), a protein that regulates synaptic vesicle trafficking and subsequently releases dopamine. Therefore, the detection and accumulation of mutated lysosomal enzymes, such as β‐GCase, in the cerebrospinal fluid might serve as biomarkers for Parkinson’s Disease.