The Role of Autophagy Pathways in Neurodegenerative Diseases: A Review

This literature review examines the crucial role of autophagy, a cellular process responsible for removing misfolded proteins and damaged organelles, in the context of neurodegenerative diseases. The review synthesizes findings from various studies, highlighting how the decline of autophagy with age contributes to the development of conditions such as Alzheimer's and Parkinson's diseases. It discusses the different types of autophagy, including macroautophagy, and their significance in protecting neural cells. The review further explores the relationship between autophagy and apoptosis, emphasizing how autophagy helps maintain cellular homeostasis and protect against waste accumulation. Contradictions regarding the effectiveness of autophagy in the elderly are also discussed, along with the potential for therapeutic interventions targeting autophagy to mitigate the severity of neurodegenerative diseases. Ultimately, the review concludes that autophagy is essential for maintaining neural cell homeostasis by eliminating toxic cellular depositions, suggesting that it could serve as a valuable therapeutic target for treating and preventing neurodegenerative disorders. The review references several studies, indicating the importance of ATG7 and ATG5 genes in the removal of aggregated wastes in neurons and the close relationship between autophagy and neurodegenerative diseases.

Running head: LITERATURE REVIEW
INVOLVEMENT OF AUTOPHAGY PATHWAYS IN
NEURODEGENERATIVE DISEASE: A LITERATURE REVIEW
Name of the Student
Name of the University
Author Note

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LITERATURE REVIEW
Abstract
The primary aim of this paper is to develop the knowledge about the autophagy mechanism and
the effectiveness of this mechanism in mitigation of the issue of the neurodegenerative diseases.
It has been found that the deposition of the dysfunctioning and misfolded, toxic proteins are the
primary cause of the development of the neurodegenerative diseases. More accurately it can be
stated that with age the decline of the autophagy leads to the development of the
neurodegenerative diseases of the aged people. Hence, the effective ways should be developed
for the regulation of the autophagy process in order to reduce the risk of the neurodegenerative
diseases. This review paper is focused on the relationship between the autophagy mechanism and
the neurodegenerative diseases.

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Introduction
Autophagy is a negative cellular networking signal that effectively eliminates the
depositions of the cytoplasm including the misfolded proteins, dysfunctioning or abnormal
cellular organelles. The mechanism of the autophsgy can be classified in three groups such as the
macroautophagy commonly known as autophagy, microautophagy and chaperon mediated
autophagy. On this context it has been seen that the process of the neuron cells are complex and
the deposition of the misfolded proteins and also the dysfunctioning cellular organelles are
reuired for these kind of cells more effectively. On this context the autophagy process is found to
be the protection of the neural cells. However, many researches highlighted that the process of
the autophagy is ineffective among the aged people thus the neurodegenerative disease rate is
higher among the aged people. In the following section the literature review would be discussed
for about the relation between the autophagy and neurodegenerative disease and the therapeutic
mechanism for reducing the severity of the disease.
Literature Review
According to Fujikake, Shin and Shimizu (2018), autophagy is the process which helps in
the degradation of the misfolded proteins and damaged organelles of cells. Hence, it is the
potential mechanism which helps in the process of eliminating unwanted materials in cell. It has
been seen that most of the neurodegenerative diseases are induced by the accumulation of
misfolded proteins in the brain cells. Thus the process of the autophagy is one of the most
effective processes which are phylogenetically inherited to encounter this issue (Bai et al., 2015).
The authors also stated that the severity of many neurodegenerative diseases has been reduced by
the autophagy process and the reduction of autophagic mechanism leads to induced severity of
the diseases such as the Alzheimer’s, Parkinson’s diseases and others (Button et al., 2017). On
this context the authors also stated that the autophagic mechanism can be classified in three
different kinds of autophagy including microautophagy, macroautophagy and chaperon mediated
autophagy. Among all these three mechanisms, macroautophagy believed to be the effective
process in the reduction of the severity of the disease as it is the mechanism which eliminates the
cellular organelles and misfolded proteins (Chen et al., 2015). However, the authors also
indicated that the process of autophagy is a catabolic process and dependent on the cellular

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stressors and the process runs by the lysosomal lytic enzymes. Hence, the association between
the autophagy and the neurodegenerative diseases are oppositely proportionate.
Based on the views of Ghavami et al. (2014), autophagy and the apoptosis are the
mechanisms which involved in the maintenance of the homeostasis of the cells and thus these
can be termed as the factors that work as protection of the cells from the waste aggregates. It has
been found that autophagic mechanism is hyperactive in the neuron cells and thus the elimination
of the aggregates such as the damaged cell organelles, membranes, proteins and others are
controlled by the authophagic mechanism. It has also been seen that the autophagy is also
regulates the apoptosis mechanism in some extents that effectively control the accumulation and
the elimination of wastes in the cell (Ghavami et al. 2012). However, it has been found that the
neuron cells are hyperactive against the accumulation of the wastes. Thus a contradiction is
evident about the effectiveness of the autophagy and the aggregates itself functions as the
neuroprotective mechanism. On this context it can be seen that the process of the autophagy is
very much ineffective in terms of the older people and the induction of the neurodegenerative
diseases such as the Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and finally
generating the amyloidogenic fragments (Cai, Yan and Ratka, 2013). Thus it is very much
evident that the autophagy is one of the mechanisms that effectively protect the neurons from
degeneration. However, the process is not so much effective in terms of the elderly people. On
this context more effective studies should be conducted in order to understand mechanism which
helps in the mitigation of the issue of aggregation of damaged organelles and proteins in the cells
which leads to neurodegenerative diseases.
Frake et al. (2015), highlighted that the most of the neurodegenerative diseases are
induced by the aggregation of the intracellular depositions and the aggregation of the aggregate
prone proteins in the cytoplasm of the neurons. On this context they also stated that the
autophagy is one of the most effective mechanisms of reducing the amount of the aggregates in
the cytoplasm. The effect of the aggregation in the cytoplasm is mainly reducing the function of
the neurons and thus the cell protection mechanism implanted for the reduction of the
aggregation. Hence, the natural system of the autophagy is one of the most effective therapeutic
processes in this case. However, there are other contradictory statements found that is the process
of the removal of these aggregations differ from autophagy. Thus the authors find other
evidences that prove the effectiveness of autophagy in this context. The authors also highlightd

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that the axon related homeostasis is controlled by the autophagical mechanism and the
elimination of this mechanism primarily affect the axonal function or leads to dystrophy. Thus it
has been seen that the autophagy-related gene 7, ATG7 and ATG5 are crucial in the removal of
the aggregated wastes in the neurons (Komatsu et al. 2007). The aggregation of the misfolded
proteins are needed to be removed and the process of the removal totally dependent on the action
of the ATG7 and ATG5. Hence, the authors concluded that the autophagy and the
neurodegenerative diseases are related closely.
Pierzynowska et al. (2018), opined that the autophagy is a process which is
phylogenetically old and conserved process in the eukaryotic cells which is controlled and
regulated by the lysosome and the lytic enzymes. This process is recognized as the aspect of
controlling the deposition in the cell and regulation of the cell metabolic factors (Menzies et al.,
2015). On this context the authors also stated that the autophagy works as a protective
mechanism against the cell deposition of the macromolecules and the long half life proteins. The
concept of the autophagy is useful in all the cells of the mammals and also other class species.
However, the malfunction or the regulatory imbalance in autophagy mechanism can be
effectively causing the induction of the metabolic neurodegenerative diseases and also other
physiological disorders (Perucho et al., 2016). On this context it has been found that the
signaling network controlling the autophagy is a negative regulation (Perera et al., 2017). Thus it
can be stated that the balance of the autophagy and other mechanisms of the cell protection is
effectively helpful in the reduction of the chances of the neurodegenerative disease chances. On
the other hand the process of the autophagy if dysfunctioned then the process of the removal of
the cell depositions would be impaired. Hence, the therapeutic process of the autophagy can be
considered as the mechanism for the treatment of the neurodegenerative diseases.
Metaxakis, Ploumi and Tavernarakis (2018), stated that the removal of the dysfunctional
and abnormal cell organelles or misfolded, toxic proteins would be required for the maintenance
of homeostasis of the neural cells. They also highlighted that the process of the removal of these
toxic substances from the cells are regulated by the mechanism of the autophagy. Hence, they
also stated that with age the function of autophagy declines and thus the process of the removal
of these toxic elements decline proportionately and lead to the induction of the
neurodegenerative diseases (Sade et al., 2016). On this context it can be stated that the regulation
or improvement in the process of the autophagy among the aged people can effectively reduce

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the risk factor of the neurodegenerative diseases. Hence, the authors reviewed some recent
evidences for supporting this mechanism or phenomena. However, there are many other theories
regarding this process although most effective and evident mechanism found to be the autophagy
process. As per the findings the authors stated that the decline in the rate of the autophagy
regulation the process of the removal of the non-functional depositions grow and thus the
induction of the neurodegenerative diseases also grow exponentially. On this context it can be
stated that the process of the regulation or control of the autophagy process would be helpful in
the elimination of the risk factor of the neurodegenerative diseases (Haghani, Shabani & Tondar,
2015).
Conclusion
Based on the above literature review it can be concluded that the process of the neural
cell homeostasis maintenance is highly dependent on the mechanism of autophagy. Hence, the
autophagy is one of the most effective processes in the controlling of the neural homeostasis by
means of the removal of the toxic and dysfunctioning cell depositions. On this context this
mechanism can be terms as the therapeutic intervention process for the neurodegenerative
disease elimination or reduction from the human aged community.

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