Role of Apolipoproteins and α-Synuclein in Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a progressive brain disorder that interferes with activities of normal life. The main pathological feature of this disease is the loss of more than 80% of dopamine-producing neurons in the substantia nigra (SN). Dopaminergic neuronal cell death occurs when intraneuronal, insoluble, aggregated proteins start to form Lewy bodies (LBs), the most important component of which is a protein called α-synuclein (α-syn). α-Syn structurally contains hexameric repeats of 11 amino acids, which are characteristic of apolipoproteins and thus α-syn can also be considered an apolipoprotein. Moreover, apolipoproteins seem to be involved in the incidence and development of PD. Some apolipoproteins such as ApoD have a neuroprotective role in the brain. In PD, apoD levels increase in glial cells surrounding dopaminergic cells. However, elevated levels of some other apolipoproteins such as ApaA1 and ApoE are reported as a vulnerability factor of PD. At present, when a clinical diagnosis of PD is made, based on symptoms such as shaking, stiff muscles and slow movement, serious damage has already been done to nerve cells of the SN. The diagnosis of PD in its earlier stages, before this irreversible damage, would be of enormous benefit for future treatment strategies designed to slow or halt the progression of PD. This review presents the roles of apolipoproteins and α-syn in PD and how some of them could potentially be used as biomarkers for PD.

Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment

“…However, it is unclear how alterations of the SNCA gene cause Parkinson disease. More recently, plasma and CSFα -synuclein has been shown to be associated with cognitive decline in PD (Emamzadeh, 2017 ) and as a potential biomarker of cognitive decline in PD.…”

Urinary proteome profiling for stratifying patients with familial Parkinson’s disease

“…They have been linked to neurodegenerative disorders including Alzheimer disease, including in our recent proteomic study of CSF [54]. APOE variants were shown to exhibit neuroprotective activity (reviewed in [65]). APOA1 is the major protein component of plasma high-density lipoprotein and its low levels in CSF and plasma have been reported as a potential PD biomarker [66][67][68].…”

Mapping the Interactive Effects of ApoE Gene Polymorphism on Caudate Functional Connectivity in Mild Cognitive Impairment Associated With Parkinson’s Disease

“…Apolipoprotein E is the most abundant apolipoprotein in the central nervous system, and its secretion by astrocytes is responsible for neuronal cholesterol homeostasis, neuronal growth, membrane plasticity, and synapse development (Emamzadeh, 2017). Recent studies have revealed that ApoE is associated with cognitive decline but not the development of PD (Peplonska et al, 2013;Multhammer et al, 2014).…”

“…Apolipoprotein E isoforms are associated with Aβ plaque deposition ( Irwin et al, 2013 ; Paul et al, 2016 ) and α-synuclein aggregation ( Emamzadeh et al, 2016 ; Emamzadeh, 2017 ) in PD, with ε4 considered to carry a higher risk than either of the others (ε2 and ε3). Paul et al (2016) and Tropea et al (2018) examined associations between genes and PD susceptibility and found that ε4 carriers exhibit faster decline than non-carriers in many neuropsychological test scores.…”