Role of neuron specific enolase as a biomarker in Parkinson’s disease

Abstract

Parkinson’s disease (PD) is thought to be the most common neurodegenerative disease with movement disorder. The key motor symptoms are rigidity, tremor, akinesis/hypokinesia/bradykinesia, and postural instability. However, in our day-to-day clinical practice we tend to see several other symptoms which may be motor or non-motor. Non-motor symptoms (NMS) are quite common and debilitating. The pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) and accumulation of unfolded or misfolded alpha-synuclein. Diagnosis of PD is difficult in the pre-motor stage. Late diagnosis renders a substantial loss of dopaminergic neurons in SNPc and spread of disease in other parts of the brain. This may manifest as either full blown symptoms requiring multiple medications or may even lead to life threatening condition due to lack of early diagnostic tools and techniques. Biomarkers are required to diagnose PD at a very early stage when prevention is possible. Hence, we see a lot of interest among researchers involved in finding a biomarker specific to the disease. Biomarkers may be clinical, image based, genetic, and biochemical. Cerebrospinal fluid (CSF) and serum markers which may correlate with disease pathophysiology are of great significance. One such molecule which recently gained a lot of attention is neuron-specific enolase (NSE). The main aim of this paper is to highlight the role of NSE in predicting neurodegeneration and neuroinflammation ultimately reflecting damage of brain cells in PD.

In Parkinson’s disease, affective and chronic fatigue syndrome symptoms are associated with neuronal damage markers

“…The most significant neuronal injury biomarker associated with MOOD and CFS symptoms in Parkinson’s disease is an increase in NSE. Increased NSE in the cerebro-spinal fluid has been suggested in some publications as a potential specific biomarker for Parkinson’s disease (Dutta, 2021). Neuronal damage (Constantinescu et al, 2009; Herrmann et al, 1999; Isgrò et al, 2015), neurodegenerative disorders such as stroke and Alzheimer’s disease (Chaves et al, 2010; Christl et al, 2019; Isgrò et al, 2015; Papuć and Rejdak, 2020), traumatic brain injury (Kim et al, 2018; Streitbürger et al, 2012), and hypoxic encephalopathy (León-Lozano et al, 2020) are all confirmed by elevated levels of NSE in serum and cerebrospinal fluid.…”

“…Neuronal damage (Constantinescu et al, 2009; Herrmann et al, 1999; Isgrò et al, 2015), neurodegenerative disorders such as stroke and Alzheimer’s disease (Chaves et al, 2010; Christl et al, 2019; Isgrò et al, 2015; Papuć and Rejdak, 2020), traumatic brain injury (Kim et al, 2018; Streitbürger et al, 2012), and hypoxic encephalopathy (León-Lozano et al, 2020) are all confirmed by elevated levels of NSE in serum and cerebrospinal fluid. Elevated NSE levels were found to be correlated with more severe depressive symptoms in children diagnosed with transfusion-dependent thalassemia (Dutta, 2021; Ridhaa et al, 2023). Conversely, adverse observations regarding serum NSE concentrations have been documented as well (Sathe et al, 2012; Schaf et al, 2005).…”

Multifunctional roles of γ-enolase in the central nervous system: more than a neuronal marker

“…In its mitochondria-bound form, enolase acts as an RNA chaperone, binding and transporting nucleo-cytoplasmic tRNAs to mitochondria. It also contributes to stabilizing mitochondrial membrane potential by binding to VDAC1, an integral mitochondrial membrane protein Prognostic and diagnostic cancer biomarker and oncotherapeutic target [ 6 , 13 , 20 , 22 , 26 – 32 ] γ-enolase Enolase 2, neural enolase, neuron-specific enolase ENO2 encodes γ subunit γγ, αγ Neurons and neuroendocrine tissue, neuronal support cells Promotes neuronal survival, differentiation, and axonal regeneration Biomarker for small cell lung cancer and neuroendocrine tumors Confirmed upregulation in neurological conditions and neurodegenerative diseases [ 1 , 14 , 22 , 26 , 33 – 42 ] β-enolase Enolase 3, muscle-specific enolase, skeletal muscle enolase ENO3 encodes β subunit ββ, αβ Muscle Distinguishes proliferating myoblasts from various stages of development, indicating β-enolase as a marker of human myoblast heterogeneity Role in cholesterol metabolism due to accelerating hepatic cholesterol ester cumulation induced via the mediation of cholesteryl ester generation Biomarker for myoblast heterogeneity that accompanies development Marker for identifying skeletal muscle injuries and the origin of bleeding Deficiency may lead to a rare inherited metabolic myopathy caused by an enzymatic defect of distal glycolysis Increased expression was detected in rhabdomyosarcoma tissue [ 12 , 21 , 22 , 26 , 43 – 50 ] Enolase 4 ENOLL ENO4 / Testis Required for normal a...…”

“…Additionally, NSE is currently recognized as the most reliable tumor marker for diagnosing, prognosing, and monitoring small-cell lung cancer [ 86 ]. NSE can be measured in cerebrospinal fluid (CSF) and serum [ 40 , 42 , 87 ]. In addition to CFS and serum NSE biomarkers, many studies have aimed to validate a plasma biomarker for neuronal damage that could be used non-invasively to study neurological diseases in both acute and chronic models [ 39 , 88 , 89 ].…”

“…Furthermore, after neuronal tissue damage, NSE levels rise sharply, correlating with injury severity and thus serving as a reliable biomarker for brain damage [42,90]. The increase in NSE levels has been observed in some neurological states, including traumatic brain injury [91][92][93][94], ischemic stroke [95][96][97][98][99][100], seizures [101,102], intracerebral hemorrhage [91,92], cardiac arrest [103][104][105][106][107], spinal cord injury [108][109][110][111][112], AD, and PD [41,[113][114][115][116].…”