Brain Disorders 3 (2021) 100020

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Brain Disorders
journal homepage: www.sciencedirect.com/journal/brain-disorders

DJ-1 and Parkinson’s disease

Ross Gibson a, Sanika P. Dalvi b, Prasad S. Dalvi a, *
a
Biology Department, Morosky College of Professions and Sciences, Gannon University, Erie PA 16541, USA
b
The University of Buckingham Medical School, Buckingham, Buckinghamshire, MK18 1EG, UK

A R T I C L E I N F O A B S T R A C T

Keywords: Parkinson’s disease (PD) is characterized by a significant loss in movement, tremors, and impaired posture.
Parkinson’s disease Worldwide prevalence of PD indicates that aging increases the risk of PD development and is more common in
Dopaminergic neurons males than females. Several environmental factors along with potential genetic factors have been found to affect
Substantia nigra
the development of PD. Most common finding in PD is degeneration of the dopamine-producing (dopaminergic)
Oxidative stress
DJ-1 protein
neurons within the nigrostriatal pathway, and neuroinflammation due to increased oxidative stress has been
PARK-7 gene associated to trigger the degeneration of these dopaminergic neurons in substantia nigra. Within the substantia
nigra, dopaminergic neurons have been well known to produce reactive oxygen species (ROS) that cause
overactivation of microglia, which are the major resident immune cells in the brain. The pro-inflammatory
cytokines produced by hyperactive microglia lead to significant neuroinflammation and degeneration of neu­
rons. Mutations in several genes also play a large role in the overaccumulation of ROS within these neurons.
Among such genes, mutations in the protein DJ-1 encoded by PARK-7 gene cause autosomal recessive forms of
PD. Several animal studies have explored DJ-1 as a possible therapeutic target for PD and neurodegeneration,
and therefore, human clinical studies that would represent an important step in unravelling the potential of DJ-1
as an ideal target for therapeutic intervention are warranted. This review attempts to describe functions and
mutations of DJ-1 and its possible roles in the pathogenesis of PD.

1. ntroduction increasingly found to play important role in its pathophysiology [3].

1.1. Parkinson’s disease
Parkinson’s disease (PD) is one of the most common neurodegener­
ative disorders mainly associated with a significant loss in movement
(bradykinesia), tremors, and impaired posture. There are many different
types of “parkinsonisms”, a generalized term described for a group of
disorders that exhibit these movement defects (Table 1). Generally,
these parkinsonisms are classified as degenerative and nondegenerative
types with the difference being that degenerative disorders are caused
by some progressive neurological degenerative process in contrast to
nondegenerative types where neuronal genetic defects play a more
prominent role. Most of these parkinsonisms carry the same or similar
symptoms with differences mainly in histological, molecular, and
neurochemical findings [1]. It is important to note that the type of
parkinsonism is quite challenging to diagnose and most often is deter­
mined post-mortem [2]. PD is the most common cause of parkinsonism
and is seen as a degenerative disorder; however, genetic properties are
Often, PD is diagnosed specifically through symptom recognition and
neuronal as well as physical examination due to present lack of a reliable
test or combination of tests that diagnose PD accurately [4]. Worldwide
prevalence of PD varies depending on the study; however, in the US and
Europe it is estimated that between 100 and 300 per 100,000 individuals
below the age of 65 develop PD, and the prevalence increases to around
950 per 100,000 individuals above the age of 65. The prevalence in
China and South America is similar to Europe and the US; however,
Africa sees a much smaller prevalence [5]. Through these prevalence
data, conclusions can be made that PD seems to increase in risk in
conjunction with age and globally varies by region. It is also found to be
more common in males than in females as 134 in 100,000 males develop
PD compared to only 41 in 100,000 females [6]. Potential genetic factors
with many environmental factors, such as, cigarette smoking and
increased exposure to pesticides increase risk of development of PD,
whereas consumption of coffee and tea potentially decrease probability
of PD development [7].

* Corresponding author at: Biology Department, Morosky College of Professions and Sciences, Gannon University, Erie, PA, 16541, USA.
E-mail address: dalvi001@gannon.edu (P.S. Dalvi).

https://doi.org/10.1016/j.dscb.2021.100020
Received 28 June 2021; Received in revised form 9 August 2021; Accepted 10 August 2021
Available online 12 August 2021
2666-4593/© 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
R. Gibson et al. Brain Disorders 3 (2021) 100020

Table 1 nigrosomes of SNr and over time the degeneration across the substantia
Classification of parkinsonism nigra increases [18].
Category Type Etiology
Nondegenerative Toxic Continued exposure to Manganese (Mn) 1.3. Factors involved in pathogenesis of PD
parkinsonism causes motor-related rigidity [1, 8]
Nondegenerative Vascular Secondary parkinsonism instigated from
Oxidative stress is caused by accumulation of reactive oxygen species
parkinsonism cerebrovascular disease such as stroke
and hypertension [1, 9] (ROS) through cellular metabolism and the diminished capability of
Nondegenerative Drug-induced Primarily related to prolonged usage of these cells to safely detoxify the oxygen radical end products in meta­
parkinsonism antipsychotic drugs, can be caused by bolism. ROS can cause a multitude of detrimental effects within cells, as
other drugs such as antiepileptic drugs their free radical properties can harm cell membrane function, alter DNA
[1, 10]
structure, and induce lipid peroxidation [19]. Dopaminergic neurons are
Degenerative Lewy body Atypical α-Synuclein protein build-ups in
dementia the brain [1, 11] specifically vulnerable to the accumulation of ROS through high iron
Degenerative Multiple system α-Synuclein protein collects in glial cells, content, increased number of mitochondria, and polyunsaturated fatty
atrophy particularly oligodendrocytes (myelin acids. Furthermore, oxidative stress can also lead to activation of glial
producing cells) causing demyelination
cells, leading to an inflammatory response [20]. The inflammatory
[1, 12]
Degenerative Progressive Tau protein lesions [1, 13]
response generated following the excess accumulation of ROS in the
supranuclear palsy neurons is known as neuroinflammation and has been proposed to
Degenerative Parkinson’s Degeneration of neurons in substantia trigger the actual degeneration of neurons (Fig. 2). Within the substantia
disease nigra and nigrostriatal pathway [14]; nigra, high concentration of activated microglia which are the major
however, genetic factors are also
resident immune cells in the brain and low density of astrocytes that
involved [3]
provide neuroprotective mechanisms by detoxification of ROS
contribute to an inflammatory state, leading to slow degeneration of the
1.2. Brain regions involved in the development of PD neurons [21]. In response to the threat of the increased ROS and the
resulting neuroinflammation, there are several mechanisms within the
PD most commonly sees degeneration of the dopamine-producing dopaminergic neurons to prevent increases of oxidative stress, such as,
neuronal cells known as dopaminergic neurons within the nigrostriatal complex III, Vitamin E, and glutathione [22, 23]. While the antioxidant
pathway (Fig. 1A), the pathway connecting the substantia nigra to the action of these molecules varies greatly depending on the mechanism,
striatum, which is the largest structure of the basal ganglia of the brain they all similarly deactivate or neutralize free oxygen radicals after their
[14]. The dopaminergic neurons, especially concentrated within the production within the mitochondria [24]. Although the antioxidant
substantia nigra, are specifically known to generate high levels of mechanisms are present within the neurons, the exact causative mech­
oxidative stress [15]. The substantia nigra lies within the midbrain and anism of neuronal degeneration in PD patients remains unknown.
functions predominantly to assist in muscle movement through release Relatively recently, protein deglycase DJ-1, also known as Parkinson
of dopamine [16]. There are two parts in the substantia nigra that differ disease protein 7 that is encoded by PARK-7 gene, was discovered to be
in both structure and function (Fig. 1B). The pars compacta of the sub­ one of the main genes that, if mutated, can be responsible for the
stantia nigra (SNc) lies dorsal and is made up of clusters of dopaminergic degeneration of these neurons [25]. Much remains to be studied about
neurons, and the pars reticulata of the substantia nigra (SNr) lies ventral the role of DJ-1 in the development of PD. In this review, we will analyze
and is composed of mostly gamma aminobutyric acid (GABA) neurons the connection between neuroinflammation and oxidative stress within
that provide inhibitory control to the local dopaminergic neurons of the PD, and the impact of the DJ-1 protein mutation and its dysfunction on
region [17]. Within the substantia nigra there are clusters of dopami­ the pathogenesis of PD.
nergic neurons called nigrosomes, and in PD, there seems to be heavy
degeneration within a nigrosome of the SNc that spreads to other

A Nigrostriatal B
pathway Superior
Colliculus
Cerebral
aqueduct

Basal Pars Ventral Pars

Ganglia Compacta Tegmental Reculata
Substana
Nigra Area

Fig. 1. (A) A schematic diagram of the intact nigrostriatal pathway showing ascending axons of dopaminergic neurons originating in the substantia nigra of the
ventral midbrain and innervating the basal ganglia (red dotted circle), (B) Transverse section through the superior colliculus of the midbrain emphasizing the pars
compacta and pars reticulata of the substantia nigra.

2
R. Gibson et al. Brain Disorders 3 (2021) 100020

A B

↑ Oxidave stress
↑ Neuroinflammaon
↓ Dopaminergic neurons
↓ Innervaon of basal ganglia
↓ Dopamine level in basal ganglia

Fig. 2. Pathogenesis of Parkinson’s disease: (A) a schematic diagram of the intact nigrostriatal pathway of dopaminergic neurons originating in the substantia nigra
and innervating the basal ganglia (red dotted circle), (B) a comparative schematic diagram of the progressive degeneration of the dopaminergic neurons (represented
by black dotted lines) that results in a loss of dopaminergic innervation of the basal ganglia and consequently leads to pathogenesis of Parkinson’s disease.

2. PD and Neuroinflammation
Neuroinflammation is the generic action of the innate immune sys­
tem to eliminate pathogens, cell debris, and misfolded proteins in neu­
rons. This inflammatory response of the central nervous system (CNS) is
a combination of all the actions of the glial cells [26]. There are three
types of glial cells within the CNS, microglia, astrocytes, and oligoden­
drocytes. Microglial cells provide most of the initial response, as they
begin in a resting state continuously scanning the brain for any abnor­
malities. When an abnormality is found through recognition of an

Fig. 3. The process of an inactive microglia activating and releasing pro-inflammatory cytokines to cause neuroinflammation that leads to degenerate a healthy
neuron. IFN-γ, interferon-γ; TNF-α, tumor necrosis factor-α; IL-1α, interleukin-1α; ROS, reactive oxygen species

3
R. Gibson et al.
Fig. 4. Chemical pathway of the degradation of dopamine leading to the generation of reactive oxygen species and the adverse effects of oxidative stress. MAO,
monoamine oxidase enzyme; DOPAC, 3,4-Dihydroxyphenylacetic acid; O2-, superoxide ion; NO▪, nitric oxide radical; ONOO-, peroxynitrite; ▪OH, hydroxyl radical
activating signal, which is usually a cytokine, the microglia undergo a
shape change, ultimately impacting their function. The activated
microglia can perform a multitude of active responses, such as, phago­
cytic action that forms a major portion of its response, synaptic stripping
which is a process of ingesting synaptic terminals to decrease sympa­
thetic input, and controlling the electrolyte efflux to regulate neuronal
metabolism and activation [27, 28]. The astrocytes control a mostly
passive response through amplification of microglial signals, but they
can also exhibit more of an active response via regulation of the meta­
bolism of neurons through control of ion channels and alterations of
neurotransmitter release [29]. Most frequently, neuroinflammation is
associated with demyelination of the axon connections within the CNS;
however, oligodendrocytes handle the remyelination of these connec­
tions during inflammatory response as the precursors of oligodendrocyte
are activated by the presence of other inflammatory cells that results in
the generation of more oligodendrocytes and the subsequent remyeli­
nation [30, 31].
In PD, neuroinflammation is specifically thought to be one of the
main causes for the degeneration of the dopaminergic neurons in the
SNc and the nigrostriatal pathway. The pro-inflammatory cytokines are
produced by overactive microglia leading to significant neuro­
inflammation [32]. There is an indication that within the sensitive re­
gions of the SNc, expression of pro-inflammatory cytokines, such as,
interleukin (IL)-1α, tumor necrosis factor-α (TNF-α), and interferon-γ
(IFN-γ) increases [33], whereas antioxidant expression, such as, gluta­
thione, decreases [34]. Investigations of the P2Y6R receptor, a receptor
located on the microglia specifically expressed during phagocytic acti­
vation, an activated state of the microglia, has been found to be present
in higher concentrations in PD patients than healthy individuals sug­
gesting a neuroinflammatory connection to PD [35]. Therefore, the
P2Y6R receptor is considered for its use as a biomarker for diagnosis of
PD. Furthermore, the use of anti-inflammatory drugs, in particular,
non-steroidal anti-inflammatory drugs, seems to reduce or even prevent
4
Brain Disorders 3 (2021) 100020
the symptoms of PD, implying the relevance of neuroinflammation
during PD pathogenesis [36]. These indications support that neuro­
inflammation within the CNS most likely contributes to the degenera­
tion of neurons associated with pathogenesis of PD (Fig. 3).
3. Neuroinflammatory response to oxidative stress
Many studies have analyzed the relationship between oxidative
stress and neuroinflammation. Due to the damaging nature of ROS, these
radicals are often utilized as a modulator of inflammatory response.
Cytokines IL-1β, TNF-α, IL-2, IL-6, and IFN-γ have all been seen to be
significantly expressed in post-mortem brain analyses of PD patients [37].
In PD and other diseases associated with excessive accumulation of ROS,
such as fibrosis and diabetes, the cytokine transforming growth factor-β
has shown to cause an increase in production of ROS, specifically
through increasing expression of an enzyme called nicotinamide
adenine dinucleotide phosphate oxidase (NOX)-4 [38, 39]. The other
forms of the NOX enzyme are also believed to be involved in the ROS
generation in humans [40]. The resulting overproduction of ROS creates
a vicious cycle eventually leading to a significant increase in neuro­
inflammatory response due to microglial activation (Fig. 3). Most
significantly, microglial activation in PD patients has been associated to
the increase in ROS production around the Lewy bodies which are
clumps of proteins that form in specific areas of the brain, in particular,
within the substantia nigra [41]. Whether the increase in ROS directly
stimulates the microglia or is mediated through increasing
pro-inflammatory cytokine production is debated; however, the relation
between the microglial activation and ROS concentrations in develop­
ment of neuroinflammation is uncontested.
4. Degeneration of dopaminergic neurons
Dopaminergic neurons have been well known to produce ROS within
R. Gibson et al.
Table 2
Overview of the most common PD genes
PD Gene Chromosomal Position
Protein deglycase DJ-1 (PARK7) Chromosome 1p36 [52]
PARK2 Chromosome 6q26 [53]
PARK8 Chromosome 12p11.2-q13.1 [54]
α-Synuclein (SNCA) Chromosome 4q21-q23 [55]
PTEN-induced kinase 1 (PINK1) Chromosome 1p35-36 [53]
Leucine-rich repeat kinase 2 (LRRK2) Chromosome 12q12 [53]
the substantia nigra. Dopamine exists in these neuronal cells within
synaptic vesicles for eventual release into the synaptic cleft to contribute
to its neurotransmitter function. When dopamine concentrations within
the neurons are in excess, they are redistributed into the cytosol. Within
the cytosol, the dopamine stability decreases significantly and triggers
degradation [42]. During this degradation of dopamine, the actions of
the monoamine oxidase enzyme produce cytotoxic ROS in the
manufacturing of H2O2 and 3,4-Dihydroxyphenylacetic acid, or the
spontaneous autoxidation of dopamine produces superoxide (O2-) ion
and quinones [43] (Fig. 4). The O2- from the autoxidation specifically
can react with nitric oxide radicals (NO▪) to create peroxynitrite
(ONOO-). ONOO- is a very reactive molecule and can cause damage
within the cell in two distinct ways [44]. Firstly, ONOO- stimulates the
nitration and the guanine oxidation of DNA, eventually creating a hy­
droxyl radical (▪OH) which results in DNA strand breakage [45]. Sec­
ondly, the ONOO- can act as a very potent oxidant, specifically targeting
thiol groups in lipids and proteins. The oxidation of these thiols results in
the production of disulfide bonds that alters the structure of these
molecules and concurrently disrupts any apparent function [45, 46]
(Fig. 4). By analyzing the breaking down of cytosolic dopamine into
ROS, it can be concluded that an excess of dopamine production within
these neurons could be the cause of neurodegeneration.
The pathological development of Lewy bodies due to accumulation
of α-Synuclein [47], and the mitochondrial dysfunction resulting in ROS
accumulation also seem to be prominent theories on the degeneration of
the dopaminergic neurons. Under pathological conditions, α-Synuclein
monomers develop toxic α-Synuclein oligomers, fibrils and
micro-aggregates, which are considered the most toxic species of
α-Synuclein, and these toxic fibril aggregates trigger the synapse
deconstruction followed by neurodegeneration [11, 48, 49]. However, it
is still unclear why the degeneration is selective for the dopamine pro­
ducing neurons in the SNc. While collectively there is plentiful evidence
of a correlation between α-Synuclein accumulation and SNc neuron
death [50], the mechanism at which the α-Synuclein specifically targets
the SNc neurons is unclear [51]. The mitochondrial dysfunction related
to the ROS accumulation within the neurons seems to be a slightly more
reliable outlook in referencing the specificity of the neurodegeneration.
Normally there is a multitude of mechanisms that counteract for the
increased ROS concentrations; however, mutations in several genes play
a large role in the over-accumulation of ROS within these neurons
(Table 2). Among such genes, mutations in PARK-7 gene lead to pro­
duction of a non-functional deglycase DJ-1 protein that prevents it from
protecting dopaminergic neurons against oxidative damage [25].
5. DJ-1 action and mutations
The PD patients have an autosomal recessive variant of the PARK7
gene; however, sometimes an autosomal dominant variation of the
leucine-rich repeat kinase 2 (LRRK2) or α-Synuclein (SNCA) genes can
contribute to the symptoms of this disorder [56]. The PARK7
gene-encoded DJ-1 protein is highly expressed in cells with high energy
demand and increased oxidative stress environment, as it is observed to
be overexpressed in most human cancers and similarly expressed in the
testis where low expression of DJ-1 is associated with infertility [57, 58].
These findings potentially suggest that the predominant action of DJ-1 is
against oxidative stress and that the overexpression of DJ-1 protects
5
Brain Disorders 3 (2021) 100020
against oxidative damage at least to some degree; however, the exact
mechanism in which the protein performs this function is still debated.
The leading suggestion of the DJ-1 protein function is that it may act as a
chaperone that assists in refolding damaged proteins, folding of new
proteins, and/or delivering damaged proteins to proteasomes [59].
Within PD rodent experimental models, dopamine producing neurons in
substantia nigra seem to show high rates of transcription of the PARK7
gene, which relates to the high amounts of ROS produced by these
dopaminergic neurons [60].
The PARK7 gene is present on chromosome 1, and mutations in the
gene are related to an autosomal recessive variant of PD. Firstly, mu­
tations in the Cys-106 residue have been observed to prevent cell growth
in high oxidative stress environments [61]; however, this mutation has
not been tested in association with PD yet and warrants further inves­
tigation. Next, frameshift mutations in exon 2, which is the first coding
exon, and exon 7 have been found to cause a complete loss of functional
DJ-1 protein in an analysis of 107 early-onset PD patients who were less
than 50 years old at the time of diagnosis [62]. The specific DJ-1 mu­
tations show differences based on ethnic origin as well. As an example, a
14bp deletion placing the centromeric border within an intron (intron 5)
was seen in Dutch/Italian patients but was not present in any other
ethnicity [63]. In eastern Indian populations and potentially present in
Western Europeans as well, an Arg98Gln variant of the DJ-1 protein has
been present in PD patients [64]. Mutations of the gene itself seem to
show significant variance between most patients; however, the muta­
tions that affect protein function substantially affect survival of cells in
oxidative environments [65]. Mutations within the DJ-1 protein have
been seen to cause an apparent loss in the function of the chaperone
action and/or the ability to protect the cells from oxidative stress,
potentially leading to PD [66]. There are a multitude of specific muta­
tions within DJ-1 protein that can be associated with PD, some more
clearly linked to PD pathogenesis than others [67].
6. Current therapies and treatments for PD
There have been many treatments tested to improve PD progression.
Currently, the main drugs are focused on controlling the symptoms of
the disorder and are prescribed based on the stages of the disorder.
Levodopa and carbidopa, or a combination of both, are used to treat the
symptoms; however, they induce some long-term consequences related
to heart rhythm, so dopamine agonists can be given in its place [68].
One notable drug tested is Bruceine D, which has been found in multiple
studies to reduce oxidative stress and decrease inflammatory response
by improving an antioxidant system regulated by E2-related factor 2
(Nrf2) [69]. The natural medicine derived from Crocus Sativus, an herb
found in countries like Iran and India, and commonly known as saffron,
has shown effectiveness in suppressing inflammatory cytokines and
ROS. Many compounds have been derived from saffron and have shown
some promise in mice studies related to neuronal injuries [68, 70].
While early on in its research, some suggestions have been made for
investigation of brain-gut peptides like glucagon-like peptide 1, pitui­
tary adenylate cyclase-activating peptide, nesfatin-1, and ghrelin due to
their neuroprotective effects on the PD symptoms [71]. Stem cell re­
placements have shown some promise in reference to neuronal diseases;
however, in vivo applications have not demonstrated as much success.
Cell transplantation therapies exhibit much promise on the effects of PD
due to the direct loss of SNc neurons being one of the main patho­
physiological features of PD. Currently, fetal ventral mesencephalic
(FVM) tissue transplantation using 6-9 week old aborted human embryo
shows the most promise, as majority of studies investigating FVM grafts
show significant reduction in typical PD symptoms while similarly
improving dopamine release [72-74].
7. Diagnostic and therapeutic potency of DJ-1 in PD
The accuracy of the clinical diagnosis in the early stages of PD is still
R. Gibson et al.
Fig. 5. Schematic diagram summarizing the roles of normal and mutant DJ-1 protein in health and pathogenesis of Parkinson’s disease (PD), and proposed diagnostic
and therapeutic potency of DJ-1 in PD.
limited. Functional neuroimaging techniques are helpful in patients with
first signs of parkinsonism, but are expensive and not broadly available.
Therefore, a priority for the scientific community is the detection of PD
pathology at early stages of the disease. In this regard, a recent study
found that the ratio of neural-derived exosomal DJ-1 levels to total DJ-1
was increased in PD patients versus controls, and a positive correlation
was found between levels of DJ-1 and α-Synuclein in plasma neural-
derived exosomes, thus indicating a potential for exosomal DJ-1 as a
PD biomarker [75]. Another study found that detection of DJ-1 in the
cerebrospinal fluid can be used as a biomarker for PD [76], however, this
potential of DJ-1 as a biomarker is still unclear, and larger clinical trials
are needed to fully validate DJ-1 as a reliable PD biomarker.
DJ-1 has been found to be therapeutically effective for animal
models of neurodegenerative disorders [77]. In some of these studies, rat
PD models were tested for the efficacy of recombinant wild type DJ-1 for
protection of dopaminergic neurons [78, 79]. Other studies adopted a
novel strategy for obtaining DJ-1-mediated dopaminergic neuronal
protection by preventing its overoxidation and thereby its inactivation
[80]. By using brain penetrant molecules able to interact with the
Cys106 region of DJ-1 that help DJ-1 maintain its active form, it was
found that these DJ-1 interactors prevented dopaminergic neuronal
death and restored normal locomotor function in rodent models of PD
[81, 82]. These and other animal studies have explored DJ-1 as a
possible therapeutic target for PD and neurodegeneration, however,
such studies using human cohorts are currently missing and need to be
undertaken that would represent an important step in unravelling the
potential of DJ-1 as an ideal target for therapeutic intervention.
8. Conclusion and perspective
PD most commonly results due to degeneration of the dopaminergic
neurons within the substantia nigra and nigrostriatal pathway. Genetics
has been found to play an important role in pathophysiology of PD by
causing neuroinflammation and degeneration of the dopaminergic
neurons in the SNc and the nigrostriatal pathway. Dopaminergic neu­
rons within the substantia nigra actively produce ROS, however, several
protective mechanisms counteract for the increased oxidative stress
among which DJ-1 protein encoded by PARK-7 gene has been found to
have a specific protective role against oxidative stress-induced neuro­
inflammation and neuronal cell death. However, mutations in PARK-7
gene lead to excessive oxidation and resulting inactivation of DJ-1
protein that prevents it from protecting dopaminergic neurons against
6
Brain Disorders 3 (2021) 100020
oxidative damage. The loss of function or even reduced function of DJ-1
trigger the onset of increased oxidative stress leading to pathogenesis of
PD. Experimental rodent PD models have demonstrated that reversal of
excessive oxidation of DJ-1 can restore its neuroprotective activity
against neurodegeneration due to overaccumulation of ROS in PD, and
inhibition of overoxidation of PD-1, and thereby its inactivation, can be
a therapeutic target for the oxidative stress-related diseases such as PD.
Furthermore, detection of DJ-1 in the cerebrospinal fluid and plasma
exosome can be used as a promising biomarker for early detection and
diagnosis for PD. Overall, future studies should be directed to establish
DJ-1 as a biomarker and to utilize DJ-1 targeting compounds that either
stabilize the active DJ-1 form or enhance DJ-1 activity to restore neu­
roprotection and reverse neurodegeneration in PD. Furthermore, clin­
ical studies using human cohorts to explore the potential of DJ-1 as a
biomarker and therapeutic target for PD are warranted (Fig. 5).
Declaration of Competing Interests
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgements
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors. The authors
wish to thank the Biology Department of Gannon University for its
financial support of the publication of this article.
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